2025 NFL Week 5 Odds and Betting Lines

We’re four weeks in, and the narratives are starting to form. The Philadelphia Eagles don’t have a hangover. They’ve displayed resilience every week, versus a tough schedule, to go 4-0.

The Detroit Lions and Buffalo Bills are ready for another run at the Eagles’ title, while the Baltimore Ravens’ aspirations appear completely derailed by injuries and a matador defense.

Get ready for Week 5 NFL odds and betting lines with a preview of the marquee matchups.

NFL Odds

View the latest NFL odds at Bovada

Thursday Night Football

San Francisco 49ers (3-1) at Los Angeles Rams (3-1)

• Start: October 2 at 8:15 p.m. ET on Prime Video
• Spread: Rams -3.5, 49ers +3.5
• Moneyline: Rams -195, 49ers +165
• Total: O/U 47

Division battles are always tough to handicap, especially with the San Francisco 49ers, who have managed to post a 3-1 record despite injuries to nearly every starter on the roster. Not to mention, all of this is happening on a short week.

The 49ers are coming off a 26-21 loss to the Jaguars, while the Rams just won 27-20 over 3-0 Indianapolis. Momentum clearly favors the Rams. However, in this AFC West division clash, the underdog has secured nine of the last 10 wins.

Sunday Afternoon

Minnesota Vikings (2-2) vs. Cleveland Browns (1-3)

• Start: October 5 at 9:30 a.m. ET on NFL Network
• Spread: Vikings -3.5, Browns +3.5
• Moneyline: Vikings -185, Browns +160
• Total: O/U 37

Another international game for Minnesota, this time in London, England, at Tottenham Hotspur Stadium versus the Cleveland Browns. Bettors should be prepared for a potential quarterback change in Cleveland. After the Browns’ 34-10 loss to Detroit, head coach Kevin Stefanski stopped short of committing to Joe Flacco as the starter. That could mean rookie QB Dillon Gabriel might get the start against a tough Vikings defensive front that is looking to rebound after a 24-21 loss to Pittsburgh in Ireland. With the Browns arguably having the most dominant defensive line in football, oddsmakers seem to expect both offences to struggle with a total of 37.

Denver Broncos (1-2) at Philadelphia Eagles (4-0)

• Start: October 5 at 1 p.m. ET on CBS
• Spread: Eagles -5.5, Broncos +5.5
• Moneyline: N/A
• Total: O/U 44.5

The Eagles have plenty of reasons to be optimistic about their post-Super Bowl start. They’ve shown the same fire as last year, are squeaking out tough wins against difficult opponents, and are even dealing with a disgruntled A.J. Brown just like during their 2024-25 run.

The only thing missing is a standout performance from running back Saquon Barkley. The 2024 offensive player of the year isn’t enjoying the same impressive start as last year; he’s averaging only 3.1 yards per carry and hasn’t had a 100-yard game this season.

Tampa Bay Buccaneers (3-1) at Seattle Seahawks (3-1)

• Start: October 5 at 4:05 p.m. ET on CBS
• Spread: Seahawks -3, Buccaneers +3
• Moneyline: Seahawks -175, Buccaneers +150
• Total: O/U 44.5

The Buccaneers’ knack for pulling out close wins came to an end in Week 4, as they fell to the Eagles by six despite clawing back from an 18-point halftime deficit. However, it doesn’t get any easier; next, they visit a Seahawks team notorious for being a tough squad at home.

Seattle has won three straight, and it appears that starting QB Sam Darnold has found his groove with the Seattle offense. Seattle’s defense has also been better than expected, averaging just 16.8 points against.

Sunday Night Football

New England Patriots (2-2) at Buffalo Bills (4-0)

• Start: October 5 at 8:20 p.m. ET on NBC
• Spread: Bills -8, Patriots +8
• Moneyline: Bills -430, Patriots +320
• Total: O/U 49.5

The Patriots are riding high after beating the Carolina Panthers 42-13. Unfortunately, they face an undefeated Bills squad who haven’t scored less than 30 points all season. Patriots QB Drake Maye looks efficient when he can lean on the run game and defense, but he’ll likely be in a shootout against Josh Allen and the Bills.

The good news? Division matchups in the AFC East tend to be closer than expected, and New England has covered four consecutive games against Buffalo, including twice when they were double-digit underdogs.

Monday Night Football

Kansas City Chiefs at Jacksonville Jaguars

• Start: October 6 at 8:15 p.m. ET on ESPN/ABC
• Spread: Chiefs -3, Jaguars +3
• Moneyline: Chiefs -175, Jaguars +150
• Total: O/U 45.5

Has Jacksonville truly established itself as a contender in the AFC? The Chiefs will be the true test of their position. The Chiefs are coming off a commanding and surprising 17-point victory over the Baltimore Ravens, as they seemed to finally recapture their potent offence combined with a solid defence. The Jaguars have managed to beat lesser teams in Carolina, Houston, and an injury-riddled San Francisco, but they have yet to prove themselves against a playoff contender like Kansas City.

All Week 5 NFL Games