NFL Week 4 – Predictions & Best Bets

Three weeks in, teams are beginning to show who they really are. Early surprises and disappointments have already shifted the betting market, and Week 4 brings another round of intriguing matchups with opportunities to spot value.

The slate features Thursday night’s NFC West showdown between the Seahawks and Cardinals, the first-ever NFL game in Dublin with Vikings-Steelers, and a primetime Packers-Cowboys clash that could carry major playoff implications. 

Elsewhere, contenders like the Bills, 49ers, and Lions look to keep momentum rolling against opponents fighting to stay in the mix.

Injuries are also shaping the storylines, with several quarterbacks and key playmakers sidelined or questionable, adding more volatility to the board and influencing lines across the market.

Below, we break down every matchup with odds and best bets for Week 4. (Odds current as of Tuesday, September 23, 2025 - lines subject to change).

Week 4 Matchups & Best Bets at a Glance

Seattle Seahawks at Arizona Cardinals

Thursday, September 25, 8:15 p.m. ET (Prime Video)

Week 4 opens in Arizona with two teams looking for consistency. Seattle has alternated strong offensive stretches with frustrating lapses, often tied to protection breakdowns.

Sam Darnold has the weapons to punish Arizona’s defense if given time, with DK Metcalf and Tyler Lockett capable of producing explosive plays. Kenneth Walker adds a rushing threat that can soften up the Cardinals’ front.

The Cardinals have shown willingness to attack vertically under their young QB, and against a Seattle defense that has leaked big plays, that strategy makes sense. Arizona’s tempo and aggressive mindset could stress a secondary still searching for answers.

Neither defense has shown an ability to close out games, and with both offenses having playmakers in space, points should come. 

With the total at 46, the over looks like the sharper play. If you’re looking to put this pick into action, consider grabbing the latest BetMGM NY promo code to maximize value on your wager.

Minnesota Vikings vs Pittsburgh Steelers (Dublin, Ireland)

Sunday, September 28, 9:30 a.m. ET (NFL Network)

The NFL’s first trip to Dublin brings unpredictability, with both teams dealing with overseas travel and an unfamiliar setting. Minnesota arrives with one of the league’s more balanced attacks, pairing a reliable ground game with Carson Wentz, who steps in as the Vikings’ starter. Justin Jefferson is still the X‑factor, and against Pittsburgh’s secondary he has the potential to tilt the game.

The Vikings’ defense has been steady against the run and stronger on third downs, giving them tools to slow a Steelers team that often struggles to sustain drives. 

Pittsburgh leans heavily on its defense, with T.J. Watt and the pass rush leading the way, but offensive red‑zone issues and inconsistent quarterback play remain concerns.

Traveling abroad tends to magnify those offensive challenges, and Minnesota’s ability to finish drives makes them look like the steadier side. As slight favorites, the Vikings’ balance on both sides of the ball makes them the safer pick in Ireland. 

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Washington Commanders at Atlanta Falcons

Sunday, September 28, 1:00 p.m. ET

The Commanders enter with uncertainty under center, limiting their offensive potential. While their defensive front remains a strength and is capable of generating pressure, the lack of consistent quarterback play has made it difficult to complement that strength with scoring.

Washington has struggled to sustain drives and too often relies on its defense to keep games competitive.

Atlanta, meanwhile, has leaned on its punishing ground attack and efficient play-action passing. Bijan Robinson continues to give the Falcons a reliable spark, and their offensive line has been able to control tempo against most fronts. Their physical style has worn down opponents, particularly at home, where they’ve built a strong advantage.

The Falcons’ defense has also shown improvement, limiting explosive plays and creating turnovers that give their offense shorter fields. 

Combined with Washington’s QB instability, those factors point to Atlanta being in position to dictate the flow of the game. Given Washington’s struggles and Atlanta’s consistency in the trenches, the Falcons’ edge in identity and execution makes them the stronger play.

New Orleans Saints at Buffalo Bills

Sunday, September 28, 1:00 p.m. ET

The Bills are among the hottest teams in football, with Josh Allen in command of an offense that can strike quickly or methodically. His chemistry with Stefon Diggs and emerging targets has kept defenses guessing, while Buffalo’s ground game has provided just enough balance to prevent teams from keying on Allen.

Defensively, the Bills have forced turnovers at a high rate and rank near the top in pressure rate, making them difficult to scheme against, especially in Orchard Park.

The Saints limp in with major injuries on both sides of the ball. Their offense has been disjointed, struggling to sustain drives without a consistent running threat and lacking explosiveness in the passing game. 

On defense, missing key starters has left them vulnerable against both the run and deep passes, forcing the unit to spend too much time on the field.

The spread is wide at nearly two touchdowns, but Buffalo’s strength in all phases justifies it. Their ability to generate big plays while limiting opponents gives them multiple paths to cover. 

In Orchard Park, the Bills are well positioned to dominate against an undermanned New Orleans squad.

Cleveland Browns at Detroit Lions

Sunday, September 28, 1:00 p.m. ET

Detroit has lived up to expectations with one of the league’s most efficient offenses.

Jared Goff continues to thrive behind a sturdy offensive line, distributing the ball across multiple weapons including Amon-Ra St. Brown and rookie contributors who have added depth. Their ground game, powered by a strong rotation of backs, forces defenses to stay honest and opens up play‑action opportunities.

The Browns are still searching for answers offensively, with inconsistency at quarterback and a lack of rhythm in the passing game making it difficult to build momentum. 

While their defense features playmakers up front and has produced strong stretches, it often wears down when the offense cannot sustain drives. Big plays allowed late in games have been a recurring problem.

At home, the Lions’ combination of elite pass protection, scoring efficiency, and the energy of a raucous Detroit crowd should tilt the matchup their way. Their ability to finish drives contrasts sharply with Cleveland’s offensive struggles, making Detroit the side to back.

Tennessee Titans at Houston Texans

Sunday, September 28, 1:00 p.m. ET

The Titans still revolve around a power rushing identity, grinding possessions and leaning on their defense. While effective in spurts, it often caps scoring output and leaves them vulnerable if they fall behind early.

Meanwhile, Ryan Tannehill has struggled to generate consistent production through the air, making Tennessee heavily dependent on Derrick Henry’s ability to set the tone.

Houston has shown flashes with C.J. Stroud, who continues to develop chemistry with his young receiving corps. 

The Texans’ offensive line has improved in pass protection, but their preference remains balance and methodical drives. Against Tennessee’s front, explosive plays may be limited, forcing Houston to execute long possessions.

Defensively, both teams have been solid against the run but vulnerable in coverage at times, which means mistakes could still swing momentum. However, with both sides preferring slower tempos and methodical football, the total at 41 feels ambitious. The under is the smarter side.

Carolina Panthers at New England Patriots

Sunday, September 28, 1:00 p.m. ET

The Panthers remain in rebuild mode with a rookie quarterback adjusting to NFL speed. Mistakes, turnovers, and growing pains have defined their early weeks, and the offense has struggled to sustain drives against stronger defenses.

Carolina has talent at receiver and a promising young defense, but inconsistency has prevented them from putting together complete performances.

New England, while not explosive offensively, has leaned heavily on its defensive discipline. Bill Belichick’s track record against rookie QBs is strong, often forcing them into mistakes through disguised coverages and well‑timed blitzes. 

But offensively, the Patriots still rely on efficiency, field position, and a strong kicking game rather than high scoring outputs.

At home in Foxborough, the Patriots’ ability to control tempo, win special teams, and minimize errors makes them the side to back against a Panthers team still learning on the job.

Los Angeles Chargers at New York Giants

Sunday, September 28, 1:00 p.m. ET

The Giants’ offense has stalled through three weeks, rookie Jaxson Dart is making his first start, and protection breakdowns remain an issue and generate explosive plays.

Protection breakdowns have limited their ability to stretch the field, and the run game has yet to take pressure off the passing attack. Against Joey Bosa and Khalil Mack, those issues could worsen as the Chargers’ pass rush looks poised to collapse the pocket.

The Chargers can score and have a high ceiling with Justin Herbert, but they’ve been inconsistent and sometimes mistake-prone, particularly when forced into long-yardage situations. Their offense tends to alternate between explosive drives and frustrating three-and-outs, giving opponents opportunities to hang around. 

New York’s defense, while not dominant, still has the talent in its front to slow Los Angeles enough to keep the game close.

With both teams showing flaws and neither side likely to run away on the scoreboard, this matchup shapes up as a lower-scoring contest. The total at 44 looks ambitious given the Giants’ offensive struggles and the Chargers’ volatility, making the under the sharper angle.

Philadelphia Eagles at Tampa Bay Buccaneers

Sunday, September 28, 1:00 p.m. ET

The Eagles haven’t hit full stride offensively but continue to stack wins thanks to their disruptive defensive front.

Jalen Hurts’ dual-threat ability remains difficult to scheme against, and when their offensive line is healthy, Philadelphia has shown they can dominate both in the trenches and on the scoreboard. Their ability to control possession and punish defenses with both the run and pass keeps them balanced even when not firing on all cylinders.

Tampa has relied on big plays but struggled with consistency, especially when drives extend into long third-down situations. Their run game has not provided much relief, putting added pressure on the quarterback to force throws against top defenses. 

Against Philadelphia’s relentless pass rush, sustaining drives and protecting the ball becomes difficult.

With a modest spread, the Eagles’ depth and defensive edge make them the trustworthy pick. Their versatility on offense and dominance in the trenches provide multiple paths to cover in what could be a physical matchup.

Indianapolis Colts at Los Angeles Rams

Sunday, September 28, 4:05 p.m. ET

Matthew Stafford continues to find rhythm with Cooper Kupp and Puka Nacua, keeping the Rams’ offense competitive even with protection concerns. Quick passing concepts and McVay’s play‑calling have helped mitigate pressure and create chunk plays downfield.

The Colts’ rookie QB has shown flashes of potential, leaning on Jonathan Taylor and play‑action to generate big gains. His athleticism adds another dimension, but mistakes under pressure remain an issue, and the defense has struggled to hold up against top quarterbacks.

With both teams capable of moving the ball and trading scores, this matchup sets up well for points. The total sits at 47.5, and given the offensive firepower on both sides, the over is the best angle.

Jacksonville Jaguars at San Francisco 49ers

Sunday, September 28, 4:05 p.m. ET

The 49ers are shorthanded after Nick Bosa’s Week 3 knee injury, leaving their pass rush reliant on depth. The 49ers’ defensive line still generates pressure with multiple contributors, and their linebackers help keep the middle of the field under control.

Offensively, Kyle Shanahan’s run-first scheme travels well, with Christian McCaffrey and a creative rushing attack keeping the chains moving.

The Jaguars continue to lean on Trevor Lawrence, but inconsistency in pass protection has limited their ceiling. Jacksonville has weapons in Calvin Ridley and Christian Kirk, yet too often Lawrence is under duress, leading to stalled drives and forced throws. 

Against San Francisco’s disciplined defense, those mistakes are likely to be magnified.

Even without star power on defense, San Francisco’s overall balance, depth, and home field advantage give them multiple avenues to cover the spread. Their ability to win in the trenches and control tempo makes them the side to back in this matchup.

Baltimore Ravens at Kansas City Chiefs

Sunday, September 28, 4:25 p.m. ET

This AFC clash pits Lamar Jackson against Patrick Mahomes, but defense may decide it.

Kansas City has quietly been one of the stronger defenses through three weeks, limiting explosive plays and forcing opponents to settle for field goals. Their secondary has tightened up, and Chris Jones continues to be a disruptive force in the middle.

But Baltimore’s front seven excels at disrupting quarterbacks and thrives in the red zone, often forcing teams into difficult third-down situations. Their linebackers have been active against both the run and short passing game, while the secondary has held up better than expected against big-play receivers.

So both offenses are capable of fireworks, but with defenses this disciplined, long drives could stall and possessions may be more methodical than fans expect. 

With a total above 50, the under offers value in what could be a more controlled, chess-match style game where field goals play a larger role than touchdowns.

Chicago Bears at Las Vegas Raiders

Sunday, September 28, 4:25 p.m. ET

Chicago’s young QB is starting to look more comfortable, and their offense has opened up with improved balance. The running game has provided some relief, helping to set up play-action opportunities and give the passing attack more rhythm.

Defensively, they’ve begun to get more pressure up front, which has helped create turnovers and shorten fields for the offense.

The Raiders meanwhile remain streaky, often relying too heavily on Davante Adams to carry their offense. When he is contained, their attack tends to stall, and they’ve struggled to finish games strong. 

Plus, defensive lapses and inconsistent quarterback play have also cost them already in close matchups.

In what oddsmakers view as nearly a pick’em, Chicago’s improved balance on offense and a defense showing signs of life give the Bears underdog value. Their trajectory points upward, while Las Vegas continues to be inconsistent, making Chicago the side with more upside.

Green Bay Packers at Dallas Cowboys

Sunday, September 28, 8:20 p.m. ET (SNF)

Dallas’ status remains uncertain with CeeDee Lamb nursing an ankle sprain; monitor his availability before betting this line. This has left Dak Prescott with fewer options on offense and forcing the Cowboys’ defense to rely more heavily on depth pieces.

The passing game has lacked rhythm at times without consistent protection or reliable receiving options, and the defense hasn’t looked as intimidating without its full complement of stars.

Green Bay, meanwhile, looks steady behind Jordan Love and a defense that has held its own. Love has shown poise and developed chemistry with his young receivers, while the offensive line has kept him upright enough to execute. Their running game has also provided balance, giving the Packers different ways to attack.

With Dallas weakened and Green Bay showing more overall balance, getting more than a field goal with the healthier, more complete team makes the Packers the right side under the lights.

New York Jets at Miami Dolphins

Monday, September 29, 7:15 p.m. ET

The Jets’ defense has elite talent but has underperformed so far in 2025. Still, it remains their best path to slowing Miami. Sauce Gardner and company should limit Tyreek Hill’s damage, and their front seven has been stout against the run.

Containing Miami entirely is unlikely, but New York has the personnel to force the Dolphins into longer drives and minimize explosive plays.

New York’s offense, however, continues to stall with instability at quarterback. The passing game has lacked rhythm, and their offensive line issues have made sustaining drives difficult. Even when they move the ball, finishing in the red zone has been inconsistent, which keeps their scoring ceiling capped.

Miami’s speed always makes them dangerous, but when paired with the Jets’ defensive strength and New York’s offensive limitations, the matchup points toward a lower total. 

With one offense elite and the other unable to finish, the under looks like the safer angle. Bettors can also compare offers at the top NY sportsbooks to get maximum value on this matchup.

Cincinnati Bengals at Denver Broncos

Monday, September 29, 8:15 p.m. ET

Cincinnati’s offense has sputtered without Joe Burrow, leaning on a backup who has struggled to create explosive plays and often looks hesitant under pressure.

While the Bengals have tried to lean more on the run game, it hasn’t been enough to offset the lack of passing rhythm, and has often left them unable to keep pace in higher-scoring situations. Their receivers remain talented, but without Burrow’s timing and accuracy, production has dipped.

Denver’s defense, on the other hand, has been disruptive at home, with a pass rush that can collapse the pocket and force turnovers. 

The Broncos have also been stout against the run, making it difficult for opponents to find balance. Playing in altitude only adds to the challenge, as visiting offenses often wear down in the second half.

With a modest line and Cincinnati struggling to find offensive answers, Denver’s defensive edge and home-field advantage make the Broncos the right side to back.

Week 4 Betting Takeaways

By Week 4, trends are beginning to solidify, but it’s still a stage where bettors can overreact to early narratives. 

Teams like Buffalo, Detroit, and San Francisco have proven trustworthy, while others such as the Jets and Giants continue to struggle offensively. 

Injuries to key starters are also shaping lines, and that volatility creates both opportunities and traps.

Totals Look Tempting

Totals stand out as sharper plays this week, particularly in games like Seahawks–Cardinals, which projects as a shootout, and Ravens–Chiefs, where defensive discipline could keep scoring in check. 

The international matchup in Dublin adds another layer of uncertainty, though Minnesota’s balance looks better suited than Pittsburgh’s for the neutral-site challenge.

Keep An Eye On Primetime Lines

Primetime clashes often draw extra public action, and this week’s spotlight games, Packers–Cowboys on Sunday night and Jets–Dolphins on Monday, could hinge on injuries and defensive dominance. 

Those spots may offer contrarian value on underdogs or unders if lines get inflated.

So before locking anything in, line shop across the best NFL sportsbooks to ensure you’re getting maximum value on every wager.

And as always, bankroll discipline is key. Focus on the matchups where market perception doesn’t align with reality, and don’t stretch plays across the full slate.