San Francisco 49ers vs Tampa Bay Buccaneers Prediction 10/12/2025 Today’s NFL Picks

The San Francisco 49ers and the Tampa Bay Buccaneers meet in week 6 NFL action from Raymond James Stadium on Sunday. We will look at this from a betting perspective and determine the best bets for this game. Here’s a San Francisco 49ers vs. Tampa Bay Buccaneers prediction.

San Francisco 49ers Recap

The San Francisco 49ers come into this game looking to build on their 26-23 win over the Los Angeles Rams last time out to improve to 4-1 this season. After this game, San Francisco will head home for a game against the Atlanta Falcons.

49ers Looking To Keep The Ball Rolling

Mac Jones has thrown for 905 yards, 6 touchdowns and an interception on 66.7% passing while Brock Purdy has thrown for 586 yards, 4 touchdowns and 4 interception on 65.8% passing. Christian McCaffrey has a team-high 282 rushing yards while also leading the 49ers in receiving with 39 grabs for 387 yards and 3 touchdowns. Ricky Pearsall has 327 receiving yards and 20 receptions while Kendrick Bourne has 229 receiving yards and two more 49ers have 100+ receiving yards as well on the year. On defense, Fred Warner has a team-high 38 total tackles and Dee Winters also had 32 total tackles and a team-high 24 solo tackles. As a unit, San Francisco’s defense has combined for 6 sacks so far this season. 

Tampa Bay Buccaneers Recap

The Tampa Bay Buccaneers come into this game looking to build on their 38-35 win over Seattle last time out to sit at 4-1 this season. After this game, Tampa Bay will head on the road for a game against the Detroit Lions.

Buccaneers Looking For Another Home Win

Baker Mayfield has thrown for 1,283 yards, 10 touchdowns and an interception on 65.1% passing while Bucky Irving has rushed for a team-high 237 yards and Rachaad White has 149 rushing yards and 3 touchdowns. Emeka Egbuka has a team-high 25 catches for 445 yards and 5 touchdowns while Irving has 193 receiving yards and 2 TDs. Sterling Shepard has 191 receiving yards and a touchdown while another pair of Bucs have 100+ receiving yards. On defense, Tykee Smith has a team-high 39 total tackles and Vita Vea has a pair of sacks. As a unit, Tampa Bay’s defense has combined for 10 sacks and 2 interceptions this season.

San Francisco 49ers @ Tampa Bay Buccaneers Betting Trends: Week 6

Why the Tampa Bay Buccaneers will win

• The Buccaneers have won each of their last four games when playing with a rest disadvantage.
• The 49ers have lost 13 of their last 16 interstate games when playing with a rest advantage.
• The 49ers have failed to cover the spread in each of their last nine Sunday games against teams that held a winning record.
• The Buccaneers have covered the spread in nine of their last 11 games as favorites when playing with a rest disadvantage.
• The Buccaneers have won the first quarter in five of their last seven home games against teams that held a winning record.
• The favorites have won the first half in seven of the last eight games between the 49ers and Buccaneers.

Why the San Francisco 49ers will win

• The 49ers have won each of their seven previous games against the Buccaneers following a road win.
• The Buccaneers have lost four of their last five October games as favorites.
• The road team has covered the spread in each of the Buccaneers’ last seven games.
• The Buccaneers have failed to cover the spread in each of their last seven home games in October.
• The 49ers have won the first half in seven of their last eight games against NFC South opponents.
• The 49ers have scored the first touchdown in nine of their last 10 games against NFC South opponents.
• The 49ers have won the first quarter in four of their last five games against teams that held a winning record.

Total Points Facts

• Each of the 49ers’ last six games played as underdogs on the East Coast have gone UNDER the total points line.
• Each of the Buccaneers’ last five games in October have gone OVER the total points line.
• Four of the last five Sunday games at Raymond James Stadium have gone OVER the total points line.

Tampa Bay Buccaneers Player Prop Facts

• Rachaad White has scored at least one touchdown in each of the Buccaneers’ last four games against NFC West opponents.
• Baker Mayfield has recorded 23+ rushing yards in each of the Buccaneers’ last four games as favorites.
• Baker Mayfield has recorded 325+ passing yards in each of the Buccaneers’ last four October games.
• Emeka Egbuka has recorded 67+ receiving yards in each of the Buccaneers’ last four Sunday games.
• Baker Mayfield has recorded 24+ completions in each of the Buccaneers’ last four October games.
• Heading into Week 6, Emeka Egbuka ranks 1st in the NFL in 20+ yard receiving touchdowns (4) this season.

San Francisco 49ers Player Prop Facts

• Demarcus Robinson has recorded 37+ receiving yards in eight of his last nine road appearances against NFC opponents.
• Brian Robinson has recorded 35+ rushing and receiving yards in each of his last 16 Sunday appearances with his team as an underdog.
• Russell Gage has scored the last touchdown in three of his last four regular season appearances with his team as an underdog.
• Brian Robinson has scored at least one touchdown in each of his last seven Sunday regular season appearances with his team as a road underdog.
• Brian Robinson has recorded 24+ rushing yards in each of his last 14 Sunday regular season appearances with his team as an underdog.
• Heading into Week 6, Eddy Pineiro has recorded the most made field goals without a failed attempt this season (11).

Matchup/League Facts

• Buccaneers – four different players have recorded 70+ receiving yards in a game this season – equal-most in the NFL, heading into Week 6.
• Buccaneers – four different players have recorded 80+ receiving yards in a game this season – equal-most in the NFL, heading into Week 6.
• 49ers – four different players have recorded 70+ receiving yards in a game this season – equal-most in the NFL, heading into Week 6.
• 49ers – four different players have recorded 80+ receiving yards in a game this season – equal-most in the NFL, heading into Week 6.

San Francisco 49ers vs. Tampa Bay Buccaneers Prediction

I’m on the 49ers here. I think the Bucs just profile better as an underdog, as they’ve had a lot of their success in the underdog role this season. The 49ers just keep finding ways to deliver this season with Mac Jones under center which are words I never thought I’d say, and the 49ers are extra rested here as well. I think the 49ers get it done. Give me San Francisco.