Philadelphia Eagles quarterback Jalen Hurts (1) prepares to throw the ball during the fourth quarter against the Tampa Bay Buccaneers at Raymond James Stadium on Sept. 28, 2025.

The opening month of the 2025 NFL season is in the books and the first slate of October games arrives with just two undefeated teams heading into Week 5. They also happen to be two of the preseason Super Bowl favorites.

The Philadelphia Eagles (4-0) and Buffalo Bills (4-0) will be challenged on Sunday if some of the early picks and predictions are to be believed. Though both teams are favorites, the Eagles (hosting the Denver Broncos) and the Bills (hosting the New England Patriots) could be in dangerous spots. The first bye weeks of the year are also here, which means there are fewer matchups on the schedule around the country. But there remain plenty of fun storylines with teams jockeying for position as separation starts to develop in the NFL standings.

The intrigue begins with "Thursday Night Football" in Week 5 as the San Francisco 49ers and Los Angeles Rams put 3-1 records on the line in an NFC West tilt. Sunday features the Seattle Seahawks (3-1) hosting the Tampa Bay Buccaneers (3-1) in another matchup of NFC contenders. There's also a crucial game between the Baltimore Ravens and Houston Texans with both teams off to 1-3 starts.

The Los Angeles Chargers (3-1) vs. Washington Commanders (2-2), perhaps with a returning Jayden Daniels, also highlights the late afternoon kickoffs on Sunday, while the Kansas City Chiefs (2-2) face the Jacksonville Jaguars (3-1) on the road in a "Monday Night Football" matchup featuring two AFC contenders to wrap up the Week 5 action.

Here is an early look at picks, predictions and odds for all of the Week 5 games on the 2025 NFL schedule:

NFL Week 5 game predictions, picks

Odds courtesy of BetMGM as of Tuesday, Sept. 30 at 2 p.m. ET.

San Francisco 49ers vs. Los Angeles Rams

  • Date: Thursday, Oct. 2
  • Time: 8:15 p.m. ET
  • Location: SoFi Stadium (Inglewood, California)
  • TV: None
  • Streaming: Amazon Prime, NFL+
  • Spread: Rams (-6)

CBS Sports: Rams 24, 49ers 17

"The 49ers are banged up, and now, they have to play a road game on a short week against a division rival that has beaten them three straight times. Also, the 49ers are going to be starting a banged-up QB and that's exactly what you don't want to do when you're about to face a Rams defense that's tied for the second-most sacks in the NFL this year. The Rams defense is going to feast."

Arizona Republic: Rams 27, 49ers 24

"The winner of this games moves to 4-1 and gets an early edge in the NFC West race. The Rams' defense will make a big play late to give Matthew Stafford and company a big win at home."

Minnesota Vikings vs. Cleveland Browns

  • Date: Sunday, Oct. 5
  • Time: 9:30 a.m. ET
  • Location: Tottenham Hotspur Stadium (London)
  • TV: NFL Network
  • Streaming: Fubo, NFL+
  • Spread: Vikings (-3.5)

Sporting News: Vikings 20, Browns 14

"The Vikings' overseas tour continues in London. Cleveland's offensive struggles continue, and quarterback Joe Flacco has two TDs and four interceptions. Will Dillon Gabriel get a shot? Minnesota will make due with Carson Wentz if he starts in place of J.J. McCarthy."

CBS Sports: Browns 19, Vikings 16

"No idea who Cleveland's starting QB is going to be on Sunday, but no matter who it is ... the Vikings have surrendered the eighth-most rushing yards in the NFL this year and the Browns need to do everything they can to take advantage of that. In two starts, (Carson) Wentz is averaging 261.5 passing yards per game, but he's also been sacked NINE TIMES. And now, he has to face the best defense in the NFL."

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Houston Texans vs. Baltimore Ravens

  • Date: Sunday, Oct. 5
  • Time: 1 p.m. ET
  • Location: M&T Bank Stadium (Baltimore)
  • TV: CBS
  • Streaming: Fubo, NFL Sunday Ticket
  • Spread: Texans (-2.5)

Arizona Republic: Ravens 23, Texans 20

"Did anyone think both the Texans and Ravens would be 1-3 at this point of the season when the NFL schedule came out? Hard to believe that one of them could fall to 1-4 on the season."

Sports Illustrated: Back the Texans

"The side to back is the Texans with the points in this spot, especially with Lamar Jackson dealing with a hamstring injury. The Houston offense has struggled this season, but so has the Baltimore defense."

Miami Dolphins vs. Carolina Panthers

  • Date: Sunday, Oct. 5
  • Time: 1 p.m. ET
  • Location: Bank of America Stadium (Charlotte, North Carolina)
  • TV: FOX
  • Streaming: Fubo, NFL Sunday Ticket
  • Spread: Dolphins (-1.5)

Sporting News: Dolphins 26, Panthers 23

"The Panthers won their only other home game, 30-0, which makes this a tough line to gauge. Miami coach Mike McDaniel remains on the hot seat – and the Dolphins are on a short week. The Dolphins were a 2-0 against the spread as a road favorite last season."

Arizona Republic: Panthers 24, Dolphins 23

"The Panthers are 0-3 on the road this season and 1-0 at home. This game is in Carolina. We'll take Bryce Young and company at home, but just barely."

New York Giants vs. New Orleans Saints

  • Date: Sunday, Oct. 5
  • Time: 1 p.m. ET
  • Location: Caesars Superdome (New Orleans)
  • TV: CBS
  • Streaming: Fubo, NFL Sunday Ticket
  • Spread: Saints (-2)

New York Post: Pick the Giants

"No one feels bad for Big Blue that they lost Malik Nabers to an ACL injury. And let’s also just call the loss of a receiver due to this injury, and an ensuing line move of two points, overly dramatic. Sure, Nabers was the biggest part of their offense. However, the Giants have just injected a new quarterback who defeated one of the Super Bowl favorites. ... This is a nightmare matchup for the Saints, who are 27th in pass block win rate and 31st in run block win rate."

Arizona Republic: Giants 28, Saints 20

"The New York Giants have hope with Jaxson Dart after a big win over the Los Angeles Chargers. The Saints? They will remain the NFC's only winless team."

Las Vegas Raiders vs. Indianapolis Colts

  • Date: Sunday, Oct. 5
  • Time: 1 p.m. ET
  • Location: Lucas Oil Stadium (Indianapolis)
  • TV: FOX
  • Streaming: Fubo, NFL Sunday Ticket
  • Spread: Colts (-7)

Sporting News: Colts 28, Raiders 21

"The Raiders are improving with Pete Carroll, and Ashton Jeanty is coming off a 138-yard performance against the Bears. On the other side, Jonathan Taylor continues to lead the NFL with 414 rushing yards. The Colts and Raiders are both good against the run, so quarterbacks Geno Smith and Daniel Jones will have to make plays. Who does that without turnovers?"

Sports Illustrated: Raiders cover

"The Las Vegas Raiders are certainly not a playoff team, but aren't as bad as the betting market is treating them. ... The Colts' offense has been fantastic this season, but they showed last week that they have a turnover issue, and Daniel Jones had moments where he looked like the quarterback of old, including a game-sealing interception."

Dallas Cowboys vs. New York Jets

  • Date: Sunday, Oct. 5
  • Time: 1 p.m. ET
  • Location: MetLife Stadium (East Rutherford, New Jersey)
  • TV: FOX
  • Streaming: Fubo, NFL Sunday Ticket
  • Spread: Cowboys (-2.5)

Arizona Republic: Cowboys 31, Jets 20

"The Cowboys are coming off a rare tie to the Green Bay Packers, 40-40. While Dallas has had its struggles, it has put points on the board this season. New York won't be able to keep up."

Sporting News: Cowboys 31, Jets 24

"How will the Cowboys use the momentum from the 40-40 tie against the Packers in Week 4? George Pickens is coming off his best game – but the defense continues to give up a league-worst 420.5 yards per game. The Jets are coming off a short week, and they'll need to generate a few turnovers. Look for the Cowboys to feed Javonte Williams against a shaky Jets run defense."

Denver Broncos vs. Philadelphia Eagles

  • Date: Sunday, Oct. 5
  • Time: 1 p.m. ET
  • Location: Lincoln Financial Field (Philadelphia)
  • TV: CBS
  • Streaming: Fubo, NFL Sunday Ticket
  • Spread: Eagles (-3.5)

Sports Illustrated: Broncos get an upset

"The Philadelphia Eagles may be 4-0, but there are a lot of signs that should concern Eagles fans. ... Not only do their underlying numbers not match their record, but now they have to take on one of the best defenses in the NFL in the Denver Broncos. ... If the defense can stand tall, the Broncos are going to be live to hand the Eagles their first loss of the season."

Arizona Republic: Eagles 27, Broncos 19

"The Broncos get to go east on a short week against an Eagles team that just finds ways to win at home. That's not good news for Denver."

Tampa Bay Buccaneers vs. Seattle Seahawks

  • Date: Sunday, Oct. 5
  • Time: 4:05 p.m. ET
  • Location: Lumen Field (Seattle)
  • TV: CBS
  • Streaming: Fubo, NFL Sunday Ticket
  • Spread: Seahawks (-3.5)

CBS Sports: Seahawks 23, Buccaneers 20

"The Bucs will be facing one of the best pass defenses that they've seen this year. Only four teams have held opposing quarterbacks to a QB rating of 76 or less and the Seahawks are one of them. Only six teams have recorded 12 or more sacks this year and the Seahawks are one of them. Only three teams have seven or more interceptions this year, and yup, the Seahawks are one of them. The Bucs haven't won in Seattle since 2009."

Sporting News: Buccaneers 28, Seahawks 27

"The Buccaneers' tough early-season schedule continues against the Seahawks, who have a little extra rest after their Thursday Night Football victory at Arizona. Both teams excel at stopping the run, and the Seahawks have generated a few more turnovers. Baker Mayfield, however, has just one interception this season. It's another dramatic finish with Sam Darnold in a battle between the No. 1 and No. 3 picks in the 2018 NFL Draft."

Tennessee Titans vs. Arizona Cardinals

  • Date: Sunday, Oct. 5
  • Time: 4:05 p.m. ET
  • Location: State Farm Stadium (Glendale, Arizona)
  • TV: CBS
  • Streaming: Fubo, NFL Sunday Ticket
  • Spread: Cardinals (-8.5)

Arizona Republic: Cardinals 24, Titans 13

"The Titans have only scored 51 points in four games. The Cardinals have lost two straight games on last-second field goals. This game won't come down to that."

Sports Illustrated: Bet Titans to cover big spread

"As bad as (the Titans) are, ... the Cardinals rank 22nd in the NFL in Net Yards per Play (-0.6). They also rank 26th in offensive success rate. This is the ultimate buy-low spot on the Titans."

Detroit Lions vs. Cincinnati Bengals

  • Date: Sunday, Oct. 5
  • Time: 4:25 p.m. ET
  • Location: Paycor Stadium (Cincinnati)
  • TV: FOX
  • Streaming: Fubo, NFL Sunday Ticket
  • Spread: Lions (-10)

CBS Sports: Bet the Lions

"The Lions were just favored at home by 10 against the Browns ‒ a team with an actually good defense and an equally comparable offense to the Bengals ‒ and it didn't stop anyone from betting on them or the Lions from covering pretty easily."

Sporting News: Lions 31, Bengals 20

"The Lions have found their offensive stride with Jared Goff – who has a 77.95 completion percentage in three games since the Week 1 loss at Green Bay. The Bengals are 0-2 against the spread as a home underdog the last three seasons – so it's a rare occasion to rise up in this situation. Detroit is 11-2 against the spread as a road favorite since 2023."

Washington Commanders vs. Los Angeles Chargers

  • Date: Sunday, Oct. 5
  • Time: 4:25 p.m. ET
  • Location: SoFi Stadium (Inglewood, California)
  • TV: FOX
  • Streaming: Fubo, NFL Sunday Ticket
  • Spread: Chargers (-2.5)

BetMGM: Pick the Commanders

"Joe Alt left Sunday’s game against the Giants with an ankle injury. That further decimates an already banged-up Chargers offensive line. If Alt and Mekhi Becton miss Sunday’s game, the Chargers’ offensive prowess likely shrinks. Conversely, Washington’s offense looked decent in Atlanta without arguably its two best players. ... Jayden Daniels’ return also provides a matchup advantage for the Commanders offense."

Yahoo Sports: Commanders cover

"Expect the Commanders to get Jayden Daniels back for this game. ... Injuries to the offensive line are going to disrupt QB Justin Herbert’s time to evaluate his options down the field and will force the Chargers to change the game plan that has gotten them off to a 3-1 start this season."

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New England Patriots vs. Buffalo Bills

  • Date: Sunday, Oct. 5
  • Time: 8:20 p.m. ET
  • Location: Highmark Stadium (Orchard Park, New York)
  • TV: NBC
  • Streaming: Peacock, Fubo
  • Spread: Bills (-7.5)

Arizona Republic: Bills 34, Patriots 20

"Can the Patriots upset the Bills on Sunday Night Football? It could happen. We just don't think Drake Maye and New England's offense can keep up with Josh Allen and Buffalo on the road."

Sports Illustrated: Bet Patriots to pull off an upset

"Drake Maye has had a fantastic start to his sophomore season. ... This has all the makings of an offensive shootout, and if the Bills aren't careful, the Patriots have a chance of pulling off an AFC East upset."

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Kansas City Chiefs vs. Jacksonville Jaguars

  • Date: Monday, Oct. 6
  • Time: 8:15 p.m. ET
  • Location: Everbank Stadium (Jacksonville, Florida)
  • TV: ABC, ESPN, ESPN2 (Manningcast)
  • Streaming: ESPN Unlimited, Fubo, Sling TV
  • Spread: Chiefs (-3.5)

CBS Sports: Chiefs 27, Jaguars 23

"The Jags are averaging 144 yards per game on the ground, which is the third-highest total in the NFL. Most of that total has come from Travis Etienne ... so if they can get Etienne going, that could be the secret to pulling off an upset here. ... Kansas City is coming off a win over Baltimore in Week 4 and will be facing the Lions in Week 6. ... The return of Xavier Worthy last week sparked a Chiefs offense that desperately needed a spark."

The Athletic: Jaguars cover

"Yes, Xavier Worthy was back last week, and (the Chiefs) lit up the Ravens, but the offensive explosion had more to do with the Ravens losing just about every defensive starter throughout the course of the game. ... It’s taken a bit, but Liam Coen and Trevor Lawrence are starting to jell and should only improve if Brian Thomas Jr. can get back on track."

This article originally appeared on USA TODAY: NFL Week 5 games, picks, odds and predictions for every matchup

Reporting by Mark Giannotto, USA TODAY / USA TODAY

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