Week 2 of the NFL season is when first impressions start to meet reality. Week 1 delivered its share of surprises and betting angles, and now oddsmakers and bettors alike are adjusting to what we’ve learned.
This slate features divisional showdowns, marquee primetime games, and plenty of opportunities to spot value. From Giants–Cowboys and Bills–Jets to the Eagles–Chiefs clash, here’s our game-by-game look at every matchup with odds and best bets.
Matchup | Date / Time (ET) | Best Bet |
Sun, Sept 14, 1:00 p.m. | Under 42 | |
Sun, Sept 14, 1:00 p.m. | Cowboys -6 | |
Sun, Sept 14, 1:00 p.m. | 49ers -3.5 | |
Sun, Sept 14, 1:00 p.m. | Under 44 | |
Sun, Sept 14, 1:00 p.m. | Dolphins -4 | |
Sun, Sept 14, 1:00 p.m. | Under 41 | |
Sun, Sept 14, 1:00 p.m. | Lions -4.5 | |
Sun, Sept 14, 1:00 p.m. | Bengals -3 | |
Sun, Sept 14, 1:00 p.m. | Under 44.5 | |
Sun, Sept 14, 4:05 p.m. | Cardinals -2.5 | |
Sun, Sept 14, 4:05 p.m. | Broncos -2.5 | |
Sun, Sept 14, 4:25 p.m. | Under 46.5 | |
Sun, Sept 14, 8:20 p.m. | Vikings -3 | |
Buccaneers at Texans | Mon, Sept 15, 7:00 p.m. | Texans -4 |
Mon, Sept 15, 10:00 p.m. | Over 46 |
Disclaimer: Odds listed above are accurate as of the morning of Thursday, September 11, 2025 (ET). NFL lines and totals move frequently throughout the week. Always check your sportsbook for the latest numbers before placing a wager. If a line or total mentioned here is no longer available, consider whether the play still makes sense at the current market price.
Sunday, September 14, 1:00 p.m. ET
Best Bet: | Under 42 — expect a grind between two run-heavy teams. |
The Rams head to Nashville after opening their season at home, facing a Titans squad that still wants to win through physicality. Tennessee’s identity remains built around its offensive line and defense, while the Rams depend heavily on Matthew Stafford’s connection with Cooper Kupp and their ability to establish the run.
Oddsmakers have set the total around 42, reflecting expectations of a slower-paced game. With both teams preferring to grind out drives rather than trade quick strikes, the under looks like the sharper angle.
Sunday, September 14, 1:00 p.m. ET
Best Bet: | Cowboys -6 — Dallas’ pass rush should be the difference. |
The Giants head to AT&T Stadium with Russell Wilson under center after his move to New York this offseason. Protecting him from Micah Parsons and the Cowboys’ front seven is the top priority, especially with LT Andrew Thomas’ Week 2 status uncertain.
Dallas opened -6, and their defense has the edge. The Cowboys are well-positioned to control the game at home.
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Sunday, September 14, 1:00 p.m. ET
Best Bet: | 49ers -3.5 — San Francisco’s depth gives them the edge. |
The 49ers travel to the Superdome with Mac Jones taking over at quarterback while Brock Purdy recovers from a turf toe injury. New Orleans will look to lean on its defensive front and home-field energy to disrupt Jones’ timing, but San Francisco’s overall depth remains tough to match.
Oddsmakers have the 49ers as 3.5-point favorites, and their balance on both sides of the ball makes them the more reliable side, even with a new starter under center. The Saints are always a tough out at home, but San Francisco’s talent advantage should carry them through.
Sunday, September 14, 1:00 p.m. ET
Best Bet: | Under 44 — two strong defenses should keep scoring in check. |
The Jets get another big divisional test at home, this time hosting Josh Allen and the Bills. Buffalo bring one of the league’s most dynamic quarterbacks, but the Jets’ defense proved last season it can hang with the NFL’s best.
With a total around 44, oddsmakers expect points, but divisional matchups in September often start slower. Given the defensive talent on both sidelines, the under is the safer angle.
Sunday, September 14, 1:00 p.m. ET
Best Bet: | Dolphins -4 — Miami’s speed creates a matchup edge. |
The Patriots travel south to face Miami in September heat, a trip that historically hasn’t been kind to New England. Their defense will try to slow Tyreek Hill and Jaylen Waddle, but few teams have the speed to keep up with the Dolphins.
At -4, Miami’s offense projects to outpace New England’s more methodical approach. The Dolphins’ big-play ability gives them the advantage.
Sunday, September 14, 1:00 p.m. ET
Best Bet: | Under 41 — expect a low-scoring, grind-it-out battle. |
Seattle head to Pittsburgh in what looks like an old-school matchup. Both teams pride themselves on physical defense and a run-first mentality, which should keep possessions long and points limited.
The total sits at 41, but with two offenses that lean conservative, the under holds value in what could be decided by field position.
Sunday, September 14, 1:00 p.m. ET
Best Bet: | Lions -4.5 — Detroit’s offense should prove too efficient. |
The Lions make their home debut against division rivals Chicago. Jared Goff has plenty of protection behind one of the league’s top offensive lines, while the Bears are still hoping their young quarterback takes a step forward.
Detroit opened as 4.5-point favorites, and their ability to score consistently makes them the more trustworthy side at Ford Field.
Sunday, September 14, 1:00 p.m. ET
Best Bet: | Bengals -3 — Burrow at home gives Cincinnati the edge. |
Two of the AFC’s brightest young quarterbacks square off as Trevor Lawrence leads the Jaguars into Cincinnati. Jacksonville continue to improve, but the Bengals’ offensive firepower is proven at home.
At -3, the line is modest for a Bengals team that thrives at Paycor Stadium. Burrow’s chemistry with his receivers makes them the side to back.
Sunday, September 14, 1:00 p.m. ET
Best Bet: | Under 44.5 — AFC North clashes usually grind low. |
The Ravens enter as heavy favorites, laying double digits at home. Baltimore’s defense is built to limit explosive plays, while Lamar Jackson and the offense can control tempo once they’re in front. Cleveland’s best chance is to lean on their defensive front and slow the game down, but if they fall behind early, sustaining long drives will be a challenge.
With the total sitting around 44.5, this still profiles as a low-scoring, possession-heavy AFC North battle. The under remains the sharper side.
Sunday, September 14, 4:05 p.m. ET
Best Bet: | Cardinals -2.5 — Arizona’s offense has the edge at home. |
Two rebuilding teams clash in Arizona, where the Cardinals are slight -2.5-point favorites. The Panthers’ young quarterback is still finding his feet, while Arizona can stretch the field with their receivers.
At home, the Cardinals have a touch more stability, which makes them worth backing in a close matchup.
Sunday, September 14, 4:05 p.m. ET
Best Bet: | Broncos -2.5 — the market believes their defense gives them the edge. |
The Broncos head to Lucas Oil Stadium as slight 2.5-point favorites, a line that reflects early confidence in their defense. Denver looked sharp up front in Week 1, and their ability to generate pressure could be the difference against an Indianapolis team still adjusting to Daniel Jones as its new starter.
The Colts will try to lean on Jonathan Taylor and the ground game to keep the Broncos’ pass rush at bay. But if Indy fall behind early, Jones may be forced into higher-risk situations — and Denver’s secondary is well positioned to capitalize. With the market leaning Denver and matchup dynamics favoring their defense, the Broncos are the side to back.
Sunday, September 14, 4:25 p.m. ET (FOX)
Best Bet: | Under 46.5 — defensive fronts could keep scoring in check. |
Two of the NFL’s premier teams meet in the marquee Week 2 matchup. While Jalen Hurts and Patrick Mahomes headline explosive offenses, both clubs have disruptive defensive lines that can dictate games. Early in the season, these heavyweight showdowns often resemble chess matches more than shootouts, with both staffs focused on limiting mistakes.
The total opened higher but has been bet down to around 46.5. Even at this number, the under still offers value given the defensive talent on the field and the likelihood of a more measured pace.
Sunday, September 14, 8:20 p.m. ET (NBC)
Best Bet: | Vikings -3 — Minnesota’s firepower should shine at home. |
Sunday night features two NFC teams trying to prove they belong in the playoff conversation. The Falcons lean on their ground game and ball control, but their secondary has struggled against elite receivers. That’s a problem against Justin Jefferson, one of the league’s most dominant wideouts.
At -3, the Vikings’ offensive advantage and home crowd make them the stronger play under the lights.
Monday, September 15, 7:00 p.m. ET
Best Bet: | Texans -4 — Houston’s young offense looks ready to roll. |
The Texans kick off Monday night with C.J. Stroud leading an ascending offense. At home, they’ll test a Buccaneers team that can move the ball but is prone to turnovers.
Laying -4, Houston have enough momentum and talent on both sides of the ball to justify the play.
Monday, September 15, 10:00 p.m. ET
Best Bet: | Over 46 — AFC West rivalry points to fireworks. |
The Week 2 finale features one of the league’s most entertaining rivalries. The Chargers and Raiders have a history of close, high-scoring battles, with both quarterbacks able to stretch the field and exploit shaky secondaries. The intensity of an AFC West game under the lights should only add to the drama.
The total is set around 46, and given the offensive talent on display, the over looks like the stronger play. Expect momentum swings, explosive plays, and a finish that could once again come down to the final possession.
By Week 2, teams begin to settle in, but it’s still a dangerous spot for bettors who overreact to opening-week results. Lines often shift based on one-game narratives, creating both traps and opportunities. Divisional matchups like Bills–Jets and Giants–Cowboys tend to play closer than expected, while marquee showdowns such as Eagles–Chiefs can carry inflated totals that invite value on the under.
It’s also worth noting that road favorites, like the Broncos in Indianapolis or the Bengals in Jacksonville, become a bigger storyline this week. History shows those spots can be profitable, but only if the matchup fundamentals support the number.
As always, bankroll discipline is key. Don’t chase every angle, target the games where market perception and matchup realities don’t quite align.
If you’re looking to put your picks into play, make sure you’re getting the best NY sportsbook bonuses and odds available. We’ve put together a guide to the top NFL betting sites you can trust, so you can compare offers and find the right book for your Week 2 bets.
