NFL Week 5 Predictions: Best Picks Against the Spread
The first bye weeks of the 2025 NFL regular season are here with Atlanta, Chicago, Green Bay and Pittsburgh all off. The first London game of the year is also on tap Sunday morning. Here’s a look at all Week 5 games with NFL odds, played Sunday unless noted.
Make sure to check out Sports Interaction’s complete list of NFL game odds, NFL futures and NFL specials and props.
San Francisco 49ers at Los Angeles Rams, Thursday
The 49ers already have more wins inside the NFC West (two) than they did all of 2024 when they were swept by the Rams, albeit only by a combined nine points. But San Francisco was upset at home out of division on Sunday by Jacksonville, 26-21, despite starting QB Brock Purdy returning from injury for the first time since Week 1. But he threw two picks, and the Niners gave it away four times. Starting WR Ricky Pearsall left injured. The Rams rallied for 27-20 home win over Indianapolis. Matthew Stafford threw an 88-yard TD pass to Tutu Atwell with 1:33 left to win. It was the longest game-winning offensive TD in NFL history in the final two minutes of a fourth quarter.
Pick ATS: Los Angeles
Minnesota Vikings “at” Cleveland Browns
Second straight Sunday 9:30 a.m. ET kickoff for Minnesota in Europe. The Vikings this past Sunday lost 24-21 to Pittsburgh in Ireland while playing a second game in a row without injured QB JJ McCarthy, who is not likely back this week. Right tackle Brian O’Neill (knee) was ruled out after exiting the game in the first quarter. Centre Ryan Kelly was evaluated for a concussion at halftime and later ruled out. Cleveland coach Kevin Stefanski hinted after Sunday’s blowout loss in Detroit that he might be ready to bench struggling veteran QB Joe Flacco for rookie Dillon Gabriel. The Browns haven’t scored more than 17 points in a game yet.
Pick ATS: Cleveland
Las Vegas Raiders at Indianapolis Colts
The Raiders frankly gave one away at home to Chicago on Sunday, 25-24, for a third straight loss. Las Vegas had four turnovers and the potential wining field-goal attempt blocked in the final seconds. The Raiders are the only team in the NFL to have not scored at least 27 points since the start of 2024. QB Geno Smith leads the NFL with seven picks. The Colts suffered their first loss on Sunday but might have proven they were for real in a late 27-20 defeat at a good Rams team. QB Daniel Jones did come back to earth a bit with one TD and two turnovers after six total TDs and no turnovers the first three weeks.
Pick ATS: Indianapolis (alt -6.5)
New York Giants at New Orleans Saints
Jaxson Dart’s regular-season NFL debut was a success for the Giants as they upset the visiting Chargers, 21-18 on Sunday, as Dart became the first QB to beat a 3-0 team or better in his NFL debut in 23 years. But the win was very, very costly as young star WR Malik Nabers tore his ACL, so his season is over. Nabers’ 127 catches were the second-most in NFL history through a player’s first 19 games. The Saints put up a fight in Buffalo on Sunday but lost 31-19. That’s now a 0-10 career mark for starting QB Spencer Rattler, one of only nine QBs since 1950 to start at least 0-10.
Pick ATS: New Orleans
Dallas Cowboys at New York Jets
Short week for the Jets as they visited Miami on Monday in Week 4. New York QB Justin Fields was cleared to play after missing Week 3 in the concussion protocol but defensive starter Jermaine Johnson was out. The Cowboys played a wild 40-40 tie on Sunday night against Green Bay. Impressive scoring 40 on that Packers defence without injured Pro Bowl WR CeeDee Lamb, who is not expected back for this one. The Cowboys are now 1-0-1 this year at home when allowing at least 37 points in a game. They were 2-36 in that scenario prior to this season.
Pick ATS: New York (alt +3)
Denver Broncos at Philadelphia Eagles
Short week for Denver after hosting Cincinnati on Monday in Week 4 with the Broncos in good shape injury wise. Really short week with the travel nearly across country and this 1 ET start on Sunday. The Eagles stayed unbeaten with a very impressive 31-25 win in Tampa on Sunday. The team is now 20-1 in its past 21 games including playoffs and has scored at least 20 points in all 21, tied for the longest streak in franchise history. Jalen Hurts has become the third QB league-wide to win 18 straight games started and finished in the last 30 seasons.
Pick ATS: Philadelphia
Miami Dolphins at Carolina Panthers
Short week for Miami after hosting the Jets on Monday in Week 4. Carolina has played pretty well in two games this year and horrendously in two — it was the latter on Sunday, a 42-13 loss in New England. It was the Panthers’ eighth game scoring fewer than 15 points since the start of 2024, tied for second-most in the league. Bryce Young is now 7-25 as a starter career. He’s clearly not the answer.
Pick ATS: Carolina
Houston Texans at Baltimore Ravens
Houston has a defence good enough to win a Super Bowl but not an offence, although the Texans did score a season-high in points Sunday in a 26-0 rout of awful Tennessee to get their first win. It was the team’s first shutout in nearly 15 years. Houston has the NFL’s No. 1 scoring defence (12.8 PPG) and No. 30 scoring offense (16.0 PPG). Baltimore has an offence good enough to win a Super Bowl but not a defence as the Ravens are a shocking 1-3 after Sunday’s 37-20 loss in Kansas City. They are allowing 33.3 PPG so far, the most in franchise history through four games. And star QB Lamar Jackson injured his hamstring in the loss. He hasn’t missed a game since he was sidelined for the final five regular-season games in 2022 with a knee injury. Cooper Rush is the No. 2.
Pick ATS: Baltimore (if Jackson plays)
Tennessee Titans at Arizona Cardinals
The Titans are truly horrific with No. 1 overall pick and QB Cam Ward taking a beating behind a porous offensive line. The team’s 10-game skid is its longest since moving to Nashville, and Sunday’s 26-0 loss to Houston was the franchise’s largest shutout defeat since 2009. Ward is the third rookie No. 1 overall pick QB to start his career 0-4 since 2021. Arizona nearly staged a huge home comeback on Thursday in Week 4 but lost 23-20 at home to Seattle for a second straight close defeat. Kyler Murray had two picks and fell to 1-12 career when he throws at least two.
Pick ATS: Tennessee (alt +10)
Tampa Bay Buccaneers at Seattle Seahawks
The Bucs played without future Hall of Fame wideout Mike Evans on Sunday and lost 31-25 at home to Philadelphia. Tampa Bay did see the season debuts of starting WR Chris Godwin and Pro Bowl offensive tackle Tristan Wirfs off injury. Chase McLaughlin hit a 65-yard field goal at the end of the first half, the longest outdoor field goal made in league history. Seattle nearly blew a big lead last Thursday in Arizona but won 23-20 on a 52-yard field goal from Jason Myers as time expired. Sam Darnold led his seventh-game winning drive the past two seasons to tie Patrick Mahomes for the most in the league.
Pick ATS: Tampa Bay
Detroit Lions at Cincinnati Bengals
Short week for Cincinnati as it played again without the injured Joe Burrow on Monday night in Denver. Detroit was dominated Week 1 in Green Bay but has done the dominating since following 34-10 win over Cleveland on Sunday. Detroit’s 137 points scored are second-most in franchise history through four games. Amon-Ra St. Brown had two receiving scores and how has six in his past three games.
Pick ATS: Cincinnati
Washington Commanders at Los Angeles Chargers
Washington played a second straight game without injured star QB Jayden Daniels on Sunday and lost 34-27 in Atlanta, but Daniels is expected back for this one. No. 1 WR Terry McLaurin also was out and not clear on him for Week 5. Daniels won’t help a struggling defence that allowed Atlanta to gain 15 or more yards on 10 plays and have a season-high 436 yards overall. The Chargers suffered their first loss of the year Sunday, 21-18, in an upset at the Giants. The Bolts were the first 3-0 team to lose to a 0-3 team since 2008. They had won an NFL-high six in a row overall. Star offensive tackle Joe Alt reportedly suffered a high-ankle sprain.
Pick ATS: Los Angeles (alt -2.5)
New England Patriots at Buffalo Bills
Sunday night game. The AFC East rivals split last year, each winning at home. Buffalo looks like the AFC’s best team at 4-0 and has won the past three by double digits after taking care of the Saints on Sunday despite playing again without defensive starter Ed Oliver and Matt Milano. Buffalo has won 14 in a row at home, one shy of the team mark set in 1990-91. This is only the third year the team has scored at least 30 points in each of its first four. The Patriots played their best game of the season on Sunday and maybe in a few seasons in a 42-13 blowout of Carolina. The 42 points were the team’s most since 2021 with young QB Drake Maye having only three incompletions.
Pick ATS: New England
Kansas City Chiefs at Jacksonville Jaguars, Monday
Yet another primetime game for Kansas City. The Chiefs saved their season on Sunday with a thoroughly impressive 37-20 win over Baltimore. Electric young WR Xavier Worthy returned from injury for the first time since Week 1 and clearly made a difference in leading the Chiefs in receiving (83 yards) and rushing yards (career-high 38). Patrick Mahomes became the youngest player with 250 career TD passes. The Jags are one of the league’s most improved teams at 3-1 following a 26-21 upset win in San Francisco on Sunday. Jacksonville had four takeaways and has an NFL-high 13 after just nine all last year.
Pick ATS: Jacksonville
