Our staff predictions for Buccaneers-49ers in Week 6

The Tampa Bay Buccaneers and San Francisco 49ers are set to engage in a battle of 4-1 teams.

Tampa Bay Buccaneers head coach Todd Bowles on the sidelines during the first half of a game against the Seattle Seahawks. / Joe Nicholson-Imagn Images

The Tampa Bay Buccaneers and San Francisco 49ers are both set to square off on Sunday at 4:25, but it won't be the heavyweight bout that it could be if both teams are healthy.

The Bucs have six players ruled out on Sunday (not counting players on IR), and the 49ers have five players ruled out (not including IR). Both teams are very similar, sitting at 4-1 after finding ways to win, and now, the 49ers will head to Tampa Bay for a gritty matchup.

Will the Bucs get it done again after numerous fourth-quarter drives? Or will the 49ers take it on the road? Our staff weighs in:

Darius Hayes, Writer: Bucs 27, 49ers 23

The Tampa Bay Buccaneers host the San Francisco 49ers in Week 6, looking to keep their momentum rolling after an impressive offensive showing last week. Baker Mayfield continues to play confident, MVP-level football, and Emeka Egbuka has quickly become one of his most trusted weapons. That connection should once again shine against a 49ers defense that’s been banged up and less dominant than usual.

Mac Jones has been solid for San Francisco this season, but with mounting injuries around him and Tampa’s defense dialing up the pressure, it could be a long afternoon for the Niners’ offense. Expect another tightly contested game, but the Buccaneers’ balanced attack and late-game execution prove decisive.

Overall record: 5-0

Collin Haalboom, Writer: Bucs 27, 49ers 17

Although the Tampa Bay Buccaneers are currently enduring an unprecedented amount of injuries to some of their best players, the San Francisco 49ers will also be nowhere near full strength for this key NFC matchup between two of the conference's best teams.

The biggest issue for Tampa Bay will be trying to slow down Christian McCaffrey in the passing game, as the linebackers within Todd Bowles’ defense have already proven to be extremely susceptible in this area. Meanwhile, CMC is having the best receiving season of his career so far and is on pace to set NFL records for a RB in receptions, receiving yards, and receiving TDs.

The good news, however, is that Tampa Bay has its starting quarterback, Baker Mayfield, healthy and ready to go. Not only that, but Mayfield has thrived amidst the chaos going on around him so far in 2025 and propelled himself into the early-season MVP discussions.

Baker has proven to be the best QB in the NFL in crunch time, and I don’t see him relinquishing that reputation against the likes of Mac Jones.

Overall record: 5-0

Caleb Skinner, Writer: Bucs 27, 49ers 21

The Tampa Bay Buccaneers and the San Francisco 49ers are set to battle for the top spot in the NFC. Both teams sit at 4-1 and are dealing with their fair share of injuries up and down their respective rosters.

The Bucs have been resilient on their way to four wins, with all wins coming on game-winning drives. Tampa Bay will have to come prepared to shut down Christian McCaffrey and exploit the 49ers' defense down plenty of offensive playmakers.

The Bucs have shown they can fight through anything to pull out a win, and I think they do so once again on Sunday to take control of the NFC.

Overall record: 4-1

JC Allen, Writer: 49ers 17, Bucs 13

The Buccaneers are once again dealing with major injuries to some of their top playmakers on both sides of the ball. Luckily, so are the 49ers. The offense will be without Luke Goedeke, Mike Evans, Bucky Irving and Chris Godwin. The defense will be down three members of their secondary, including Zyon McCollum.

If the Bucs are going to win this game, starting fast on offense will be crucial, as points will likely be hard to come by. Controlling the time of possession by moving the chains and keeping the clock running should also work in the Buccaneers' favor. However, winning the turnover differential will be paramount. The Bucs' one loss this season is also the only game the Bucs lost the turnover battle.

It will be a tough test for the banged-up Bucs, as the 49ers have had their number over the past several years. Unfortunately, the injuries prove too much to overcome for Tampa Bay and they drop to 4-2 in the season.

Overall record: 4-1

Dustin Lewis, Editor: Bucs 24, 49ers 17

I kind of nailed it last week, predicting Baker Mayfield to have a major bounce-back performance against Seattle. Mayfield did more than that, though, inspiring the Tampa Bay Buccaneers to a tough road victory despite being shorthanded on both sides of the ball.

Even with Mike Evans, Chris Godwin, and Bucky Irving out along with multiple starters on the offensive line, Mayfield’s moxy always gives the Buccaneers a chance.

San Francisco will be rolling with a backup quarterback in Mac Jones. However, the 49ers have won all three games that Jones has started this season.

In the end, Mayfield is wearing red and pewter. That’s the difference on Sunday as Tampa Bay continues its hot start.

Overall record: 5-0

River Wells, Editor: Bucs 23, 49ers 17

This is a tough one to pick. The 49ers are more injured than the Bucs (somehow) and playing with a banged-up backup quarterback, but Todd Bowles hasn't bested Kyle Shanahan as head coach of the Bucs just yet and there are plenty of matchups for the 49ers to exploit on Sunday.

I think Bowles' streak changes on Sunday, though. The Bucs have been able to find ways to win, and they'll do so again against a hobbled 49ers team. If Bowles' defense can key in on Christian McCaffrey and Josh Grizzard's offense can start fast and find the red zone, the Bucs will come out of this with a win.

Overall record: 3-2

READ MORE: Buccaneers could benefit as 49ers miss three starters at practice

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