How long can Baker Mayfield keep this up?
Mayfield – who has 1,283 yards, 10 TDs and one interception through a 4-1 start – is in the top five in the NFL MVP discussion, but the Buccaneers remain a fringe Super Bowl contender in a loaded NFC that feature four other one-loss teams in Philadelphia (4-1), Detroit (4-1), San Francisco (4-1) and Green Bay (2-1-1).
Mayfield has led the Buccaneers to four victories in fourth-quarter comeback and game-winning situations this season – an astounding run where Tampa Bay has won those four games by a combined total of nine points.
There is another chance to prove the doubters wrong in Week 6. The Buccaneers face the 49ers – who have weathered injuries and still have a quarterback question with Brock Purdy (toe) still rehabbing an injury. Mac Jones is coming off a 342-yard performance in a 26-23 overtime victory against the Rams in Week 5.
Tampa Bay is fun so far – and not just because of those throwback uniforms we will not see again until Week 15. Mayfield – the No. 1 pick who went through the Browns, Rams and Panthers before arriving in Tampa Bay – is the reason why.
The 49ers-Buccaneers' matchup is among the highlights of a schedule that features a Sunday Night Football matchup between the Chiefs and Lions and another tough game for the Ravens against the Rams. The Vikings and Texans are on a bye week.
Straight up: 49-27-1 (6-7 in Week 5)
Against the spread: 41-34-2 (10-3 in Week 5)
POWER RANKINGS: Eagles, Bills fall behind 49ers, Lions; Patriots, Colts, Broncos leap for Week 6
Here are our straight-up picks for Week 6.
NFL picks, predictions for Week 6
- Philadelphia Eagles (-7.5) at New York Giants
Thursday, 8:15 p.m.
The Eagles average 73 rushing yards per game the last three weeks – and Saquon Barkley averages 39.7 yards per game in that stretch. Barkley had 176 yards against New York in Week 6 last season. Jaxson Dart gets his first prime-start, but it will be a get-well game for the Eagles. Philadelphia is 2-2 S/U at New York under Nick Sirianni.
Pick: Eagles 28, Giants 13
MORE: How Eagles lost first game of season to Broncos
- Denver Broncos (-7.5) at. New York Jets
Sunday, 9:30 a.m.
The Jets are the only winless team in the NFL. Justin Fields took five sacks in the Week 5 loss to the Cowboys – and the Broncos had six sacks against the Eagles last week. Nik Bonitto leads the NFL with seven sacks. Still, Denver is 1-1 ATS as a road favorite of seven points or more. Does London count? Will Fields get enough protection in this game?
Pick: Broncos 24, Jets 17
MORE: Jonathan Taylor, Josh Allen among NFL quarter-season favorites
- Arizona Cardinals at Indianapolis Colts (-5.5)
Sunday, 1 p.m.
The Cardinals are coming off a mistake-filled loss to the Titans – but they do have a solid run defense that allows 92.4 yards per game. The Colts have zero turnovers in their four victories, and Daniel Jones has taken just two sacks in those games. Jonathan Taylor is coming off his second three-TD performance of the season, and Indianapolis is 3-0 ATS as a favorite. Every Arizona' game has been decided by five points or less.
Pick: Colts 28, Cardinals 23
MORE: A complete beginners' guide to betting on the NFL in the U.K.
- Los Angeles Chargers (-5.5) at Miami Dolphins
Sunday, 1 p.m.
The Chargers are on tilt here after averaging just 14 points per game the last two weeks. Offensive line injuries, including tackle Joe Alt (ankle), have impacted the front line. Los Angeles is 4-2 S/U in games where they travel three time zones under Jim Harbaugh. Miami, however, might be in a worse free-fall under Mike McDaniel right now with the worst run defense in the league (174.2 ypg.)
Pick: Chargers 23, Dolphins 15
- New England Patriots (-3.5) at New Orleans Saints
Sunday, 1 p.m.
Are the Patriots a real threat under first-year coach Mike Vrabel? New England won two AFC East games on the road, and Drake Maye has a 77.3% completion percentage in those games. New Orleans forced five turnovers against the Giants in Week 5. That won't be as easy knowing the Pats have a -1 turnover differential.
Pick: Patriots 25, Saints 18
Pick: Patriots win 23-20 but fail to cover the spread.
MORE: How Stefon Diggs led upset win for Patriots over former Bills team
- Cleveland Browns at Pittsburgh Steelers (-5)
Sunday, 1 p.m.
Dillon Gabriel did not make any major mistakes in his debut as a starter – but the Browns will have to take more chances on the road against Pittsburgh. The Steelers had a week to rest from their London trip. The Browns did not. Opposing QBs have 10 TDs and no interceptions against Cleveland this season. Aaron Rodgers can work with that. The Steelers have won the last four home meetings by an average of 10.7 points per game.
Pick: Steelers 26, Browns 16
MORE: Dillon Gabriel proves he's a gamer in NFL debut loss to Vikings
- Dallas Cowboys (-3.5) at Carolina Panthers
Sunday, 1 p.m.
Are the Cowboys a NFC playoff contender? Running back Javonte Williams is coming off a 135-yard performance. Carolina running back Rico Dowdle – who played for Dallas from 2020–24 – had a breakout game with 206 rushing yards in Week 5. The Panthers are the classic home-and-road team, and this one is at home.
Pick: Cowboys 31, Panthers 26
MORE: Rico Dowdle enjoys career day in comeback win over Dolphins
- Seattle Seahawks (Pick 'em) at Jacksonville Jaguars
Sunday, 1 p.m.
The Jaguars are coming off a short week – but they have been a tough out at home. The Seahawks are 2-0 on the road. Sam Darnold has a 73.1% completion percentage, which is much higher than Trevor Lawrence. Both run defenses are good here, and the Seahawks are 9-1 S/U on the road in their last 10 games.
Pick: Seahawks 24, Jaguars 21
- Los Angeles Rams (-7.5) at Baltimore Ravens
Sunday, 1 p.m.
The Ravens are an injury-riddled mess that are teetering on falling out of the AFC playoff race. That begs the question whether Lamar Jackson (hamstring) will return against the Rams. Baltimore has a -6 turnover ratio through its three-game losing streak. It's tough to make this pick knowing whether Jackson will play, but the Ravens have to show something on defense first.
Pick: Rams 31, Ravens 28
MORE: Why the Ravens' playoff chances are already over in 2025
- San Francisco 49ers at Tampa Bay Buccaneers (-2.5)
Sunday, 1 p.m.
This is the best game in the early slot. San Francisco in a battle of 4-1 teams. Mayfield continues to shine in late-game situations, but he's been even better in the middle two quarters with seven TDs and no interceptions. Mac Jones has a 100 QB rating or better in two of three starts in place of Brock Purdy, and San Francisco is 3-0 S/U on the road.
Pick: Buccaneers 27, 49ers 23
- Tennessee Titans at Las Vegas Raiders (-6)
Sunday, 4;05 p.m.
Maxx Crosby has two sacks through five games for the Raiders, who have been turnover-prone on offense. The Titans rank 29th in the NFL in rushing offense, which hasn't helped rookie quarterback Cam Ward. Ashton Jeanty is primed for a huge game against the Titans' maligned run defense.
Pick: Raiders 27, Titans 19
- Cincinnati Bengals at Green Bay Packers (-14)
Sunday, 4:25 p.m.
The Bengals are last in the NFL in total yards per game (228.6), and Jake Browning has thrown eight interceptions. Green Bay is coming off a bye week, and there is a lot to prove after a brutal two-week stretch against the Browns and Cowboys. Green Bay is 2-0 ATS at home, but this line looks high knowing the history of bizarre finishes between these teams. The last six meetings have been decided by seven points or less.
Pick: Packers 28, Bengals 21
- Detroit Lions at Kansas City Chiefs (-1)
Sunday, 8:20 p.m., NBC
This might be a pick ‘em by kickoff given how well the Lions have played since the Week 1 loss against Green Bay. The Chiefs' front-loaded schedule continues, and Detroit has taken advantage of a plus-seven turnover ratio the last four games. The Lions beat Kansas City 21-20 in the 2023 season opener – so the confidence is there.
Pick: Lions 30, Chiefs 24
- Buffalo Bills (-3.5) at Atlanta Falcons
Monday, 7:15 p.m.
Did the Patriots show the blueprint for slowing down the Bills? It was more about penalties and turnovers, and Josh Allen should be able to clean that up on the early Monday Night Football stage. Atlanta is 2-0 S/U at home this season, and coming off a bye week, so this won't be easy.
Pick: Bills 31, Falcons 22
MORE: Who has thrown the most interceptions in NFL this season?
- Chicago Bears at Washington Commanders (-4)
Monday, 8:15 p.m.
The Commanders recalibrated their season with the return of Jayden Daniels, and the impact of Jacoby Croskey-Merritt – who had 14 carries for 111 yards and two TDs – opens up exciting possibilities in the running game. Chicago is 2-6 S/U on Monday Night Football since 2020. This is the rematch from last year's Hail Mary finish, which Washington won 18-15.
Pick: Commanders 32, Bears 25