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Tampa Bay Buccaneers vs San Francisco 49ers Predictions, Odds and Best Bets For Week 6 of the 2025-26 NFL Season

Eric Divakaran
American Football / NFL
12/10/2025 – 21:25
Tampa Bay Buccaneers
VS
21:25
12/10/2025
San Francisco 49ers
Odds updated on October 11, 2025 at 6:09 pm

The Tampa Bay Buccaneers will host the San Francisco 49ers for a Week 6 clash. This NFC South vs NFC West clash will feature two of the best NFC teams going at each other, in a potentially low scoring clash. The Buccaneers have remained hot this season, with Baker Mayfield leading the way. They got themselves a gritty win in Week 5, beating the Seattle Seahawks even with multiple injuries to their team. The Bucs have been resilient this season and are currently leading the NFC South division with a 4-1 record.

Meanwhile, the San Francisco 49ers have also been struggling with injuries to multiple players on their roster. However, even they have managed to stay afloat, leading the NFC West division with a 4-1 record. The 49ers had a statement win against the Los Angeles Rams in Week 5, and despite all the injuries, they still beat the Rams who are considered to be some of the best teams in the NFL. In week 6, multiple players are not going to participate with Brock Purdy listed as out and even their backup QB Mac Jones is questionable to start.

Game Details

  • Time: 4:25 p.m. ET
  • Date: October 12, 2025
  • Venue: Raymond James Stadium, Tampa, Florida
  • TV: CBS
  • Streaming: NFL+

Recommended Bets and Updated Odds

Recommended BetsFanDuelBetMGM
Christian McCaffrey anytime TD scorer-180-160
Rachaad White anytime TD scorer-120-175
Baker Mayfield Over 33.5 passing attempts-130-105
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Rationale and Analysis

While the Buccaneers have a stout run defense, ranking 8th overall, Christian McCaffrey is still a threat to score a TD since the 49ers are heavily reliant on him to make plays. McCaffrey has at least had 13 or more rush attempts in every game, and he has also been a go-to pass target for his quarterback. His sheer volume of touches he gets in every game makes us believe that he is a threat to score a TD at anytime, despite a slow start to McCaffrey’s season.

Rachaad White is a threat to score at any given moment because of his recent explosion against the Seahawks in Week 5 where he scored two TDs. White is also a threat because of the 49ers’ rushing defense, which has fallen off since week one, sitting 15th overall. While the Bucs have a pass-heavy offense, looking at the 49ers’ run-defense, coach Todd Bowles might decide to switch it tonight.

Baker Mayfield has at least attempted 29 or more passes in every game he’s played thus far, and looking at the 49ers’ mediocre secondary, we believe his passing attempts will go over 33.5. The Bucs also have suffered multiple injuries with both Mike Evans and Chris Godwin out for the game, and we expect Mayfield to take it upon himself and try to do more with the ball in this game.

Buccaneers vs 49ers Prediction

We expect the Tampa Bay Buccaneers to take down the 49ers in this game simply because the 49ers have way too many of their offensive and defensive weapons on the injury report, thoroughly crippling the 49ers’ chances. While we expect this game to be a very close matchup, Baker Mayfield should be able to do enough damage to the 49ers, and the Bucs are also great defensively, ranking 11th overall, which should be able to contain Christian McCaffrey’s run game.

Prediction: Buccaneers win the game 23-20

Week 6 Buccaneers vs 49ers Betting Odds and Spread

Looking at the spread and the moneyline, the Buccaneers should be able to beat the 49ers, according to BetMGM

TeamsSpreadTotal PointsMoneyline
49ers+3 (-102)47.5 (-105)+145
Buccaneers -3 (-118)47.5 (-115)-175
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Buccaneers vs 49ers Best Bets

Here are over/under and best player bets for the Tampa Bay Buccaneers and the San Francisco 49ers, as per BetMGM

Tampa Bay Buccaneers Over/Under Odds

Below listed are over/under for the Tampa Bay Buccaneers, as per BetMGM

Over/UnderOverUnder
Baker Mayfield passing yards 244.5 (-115)244.5 (-115)
Emeka Egbuka receiving yards75.5 (-115)75.5 (-115)
Rachaad White rushing yards60.5 (-115)60.5 (-115)

Tampa Bay Buccaneers Best Player Bets

Here are some of the best player bets for the Tampa Bay Buccaneers, as per BetMGM

  • Rachaad White anytime TD scorer: -175
  • Baker Mayfield over 1.5 passing TDs: -165
  • Emeka Egbuka over 5.5 receptions made: -140

San Francisco 49ers Over/Under odds

Below listed are over/under for the San Francisco 49ers, as per BetMGM

Over/Under BetsOverUnder
Mac Jones passing yards251.5 (-115)251.5 (-115)
Christian McCaffrey receiving yards52.5 (-110)52.5 (-118)
Christian McCaffrey rushing yards54.4 (-115)54.4 (-118)

San Francisco 49ers Best Player Bets

Here are some of the best player bets for the San Francisco 49ers, as per BetMGM

  • Christian McCaffrey over 15.5 rushing attempts: -130
  • Christian McCaffrey anytime TD scorer: -160
  • Mac Jones passing TDs under 1.5: -140
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(According to BetMGM: BetMGM offers exclusive promo codes, bonus deals and accurate odds for users upon signing up. Use BetMGM to ace your betting game in all sports!)

FAQs

Who is favored to win between the Buccaneers and the 49ers?
The Buccaneers are the slight 3-point favorites to win the matchup against the 49ers.

What is the over/under total for the game?
The over/under for total points is set at 47.5.

What is the predicted score for the Buccaneers vs 49ers game?
We expect the Buccaneers to take down the 49ers in a close game, with the final score of 23-20.

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I cover the National Football League and things cannot get better than that. I always dreamed to play football or basketball professionally since I’m built like a Running Back. But now that I can’t, since I’m technically in the “Unc” age, I thought why not pick a career in sports industry? So here I am, doing what I love, and hoping that the Commanders win the Super Bowl. I give love to players when it’s due, but can be critical about their performances at the same time. Enough about me, now let my articles do all the talking. 

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