The NFL’s prime-time slate in Week 5 kicks off with a Thursday Night Football battle between NFC West rivals, while the Sunday Night Football matchup showcases two AFC East foes.
The common thread in these divisional contests? Both home teams are big favorites, but a couple of strong NFL betting trends suggest that both road underdogs are more likely to pad your wallet.
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Meanwhile, the defending Super Bowl champs continue to be a spread-covering machine (although not so much at home). And an AFC franchise that has been a perennial punchline is looking to improve to 4-1 for the first time since the year the iPhone debuted.
These are just a few of the NFL betting trends we’re breaking down for the five marquee matchups on the Week 5 docket.
All listed odds are via BetMGM and subject to change.
San Francisco 49ers at Los Angeles Rams (-5.5, 47)
Kickoff: Thursday, 8:15 p.m. ET
Moneyline: 49ers +200/Rams -250
• The Rams have recently taken back some control in this rivalry, ripping off three consecutive victories (all as underdogs). Throw in a 30-23 loss as a 7.5-home underdog back in Week 2 of the 2023 season, and Los Angeles has cashed in four straight meetings.
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Prior to that, San Francisco had won and covered 15 of 20 head-to-head clashes dating to 2013, when the Rams were still in St. Louis.
Perhaps the most interesting NFL betting trend as it pertains to this rivalry: The underdog is on an 11-1 ATS roll (including the 2021 NFC Championship Game).
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• 49ers running back Christian McCaffrey was held to a season-low 49 rushing yards in Sunday’s 26-21 home loss to Jacksonville. McCaffrey has now been limited to 55 rushing yards or fewer in six of his last eight games, including three in a row.
This week, the two-time All-Pro will butt heads with a Rams defense that has allowed only two players to top 60 rushing yards: Houston’s Tony Pollard (92 yards in Week 2) and Indianapolis’ Jonathan Taylor (76 yards last week).
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McCaffrey’s rushing output in four career games against L.A.: 69, 94, 116 and 128 yards. His projection for Thursday’s contest: opened at 60.5 and is down to 57.5.
• Rams WR Puka Nacua leads the NFL with 42 receptions and 503 yards (nobody else has more than 34 catches and 402 yards). Nacua has had at least eight catches and 91 yards in every game, reaching double digits in receptions and clearing 110 yards three times.
His numbers in three career games against San Francisco: four catches, 41 yards; seven catches, 97 yards; 15 catches, 147 yards.
BetMGM has Nacua pegged for 8.5 receptions and 95.5 yards on Thursday Night Football.
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Denver Broncos at Philadelphia Eagles (-3.5, 44)
Kickoff: Sunday, 1 p.m. ET
Moneyline: Broncos +170/Eagles -210
• The Eagles freight train keeps barreling down the tracks. After holding on for a 31-25 victory at Tampa Bay in Week 4, Philadelphia improved to 22-3 since the start of last season (postseason included).
During this sensational run, Philadelphia is 17-8 ATS (68%), which includes 12-3 ATS when laying six points or less.
Then again, Philadelphia has been a money burner at home lately. Since Week 13 of the 2023 campaign, the Eagles are 7-9 ATS at Lincoln Financial Field.
• The Eagles are perfect through four weeks for the third time in the last four years. In the previous two instances, Philadelphia started 5-0 (2023) and 8-0 (2022).
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Meanwhile, the Broncos (2-2) have been above .500 five weeks into a season just twice since 2018. They were 3-2 in 2021 and rallied from an 0-2 start last year with three straight wins.
One NFL betting trend worth nothing in this non-conference clash: Denver is just 7-24 in its last 31 road games (playoffs included), including a current four-game slide. The team’s corresponding point-spread record: 11-19-1.
• Eagles running back Saquon Barkley, who last year became the ninth player in NFL history to join the 2,000-yard rushing club, has cracked 60 yards just once in four games (he had 88 at Kansas City in Week 3).
In 17 games last season, Barkley gained fewer than 65 yards just once (47 against Cleveland).
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Denver allows 99.5 rushing yards per game (11th-best in the NFL). The only two opponents to top 60 rushing yards versus the Broncos: Chargers rookie Omarion Hampton (70) and Colts star Jonathan Taylor (165).
Barkley’s over/under for rushing yards at BetMGM is 75.5.
Washington Commanders at Los Angeles Chargers (-2.5, 48)
Kickoff: Sunday, 4:25 p.m. ET
Moneyline: Commanders +125/Chargers -150
• After kicking off the 2025 season with a three-game SU and ATS winning streak, the Chargers went to New York as a 6-point favorite in Week 4 and fell 21-18 to the previously winless Giants.
The loss snapped Los Angeles’ six-game ATS regular season winning streak, but the Bolts have still paid off in 12 of their last 15 contests (5-2 ATS at home). Last time they failed to cash in back-to-back weeks? The final two games of the 2023 season.
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• With their 34-26 loss at Atlanta in Week 4 as a 2.5-point underdog, the Commanders are now 0-for-2 outside of Washington, D.C. They have now failed to cover in five consecutive regular-season road games (0-3 ATS as a road underdog).
The under is also 4-1 in those five contests, the outlier being last week’s game against the Falcons.
• Entering Week 5, the Chargers rank in the top five in the NFL in scoring defense (fourth), total defense (third) and passing defense (fifth). However, they’re middle of the pack against the run (16th).
That bodes well for Washington, which boasts the league’s second-best rushing attack, averaging 154.8 yards per game. Four Commanders have compiled at least 85 rushing yards, including QB Jayden Daniels (who has missed the last two games with a knee injury).
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Four QBs — the Chiefs’ Patrick Mahomes, the Raiders’ Geno Smith, the Broncos’ Bo Nix and Giants rookie Jaxson Dart — have combined for 164 rushing yards against Los Angeles on 29 carries (5.7 yards per rush).
New England Patriots at Buffalo Bills (-7.5, 46.5)
Kickoff: Sunday, 8:20 p.m. ET
Moneyline: Patriots +325/Bills -425
• The Bills are 4-0 for the first time since 2020 (and second time since 2009).
The last time Buffalo opened a season on a five-game winning streak: 1991, the same year the franchise suffered the second of its four consecutive Super Bowl defeats.
• During the Tom Brady era (2001-19), the Patriots went 34-4 against Buffalo (22-13-3 ATS).
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Since 2020, Buffalo has won seven of 10 meetings, but only cashed four times. In fact, these AFC East rivals split their season series the past two years, with New England covering in all four clashes.
Then there’s this NFL betting trend: The Patriots are 4-1 ATS in their five visits to Buffalo since 2020 — and 17-5-1 ATS in Orchard Park, N.Y., since 2002.
• Buffalo failed to cover double-digit point spreads the past two weeks against Miami (31-21 win as an 11.5-point favorite) and New Orleans (31-19 win as a 14.5-point chalk).
Going back to Week 6 of the 2023 season, the Bills are 4-11 ATS when laying 6 points or more in the regular season (including 0-3 ATS vs. New England).
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Kansas City Chiefs (-3.5, 46.5) at Jacksonville Jaguars
Kickoff: Monday, 8:15 p.m. ET
Moneyline: Chiefs -175/Jaguars +145
• Jacksonville (3-1) is off to its best start since the 2018 team won three of its first four contests (on the way to a 5-11 record). If the Jaguars score an upset Monday night, they’ll improve to 4-1 SU for the first time since 2007 and 4-1 ATS for the first time since 2002.
Meanwhile, the Chiefs have followed up season-opening losses to the Chargers and Eagles with back-to-back SU and ATS triumphs.
That is noteworthy heading into this Monday Night Football game for this reason: Kansas City has covered the point spread in three straight regular season games just twice since the start of the 2022 campaign.
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• Including a 2022 playoff matchup, the Chiefs are riding an eight-game winning streak against Jacksonville and are 7-2 ATS in the last nine head-to-head battles.
What’s more, since Patrick Mahomes took over as the starting quarterback, Kansas City is 5-0 SU and 4-1 ATS versus the Jaguars. Victory margins: 16, 14, 10, 8 and 7 points.
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• No Kansas City running back has rushed for more than 45 yards in a game this season. In fact, Mahomes still leads the team with 130 rushing yards.
In related news, Jacksonville fields the NFL’s fourth-best run defense, yielding just 82.8 yards per game. The leading rusher against the Jaguars so far? Carolina’s Chubba Hubbard, who rumbled for 57 yards in Week 1.
No other opposing player has reached 50 rushing yards against the Jags.
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