Tampa Bay Buccaneers vs San Francisco 49ers Picks and Predictions October 12th 2025

Tampa Bay Buccaneers vs San Francisco 49ers October 12th 2025

In Week 6 of the 2025 NFL season, the San Francisco 49ers will travel to Raymond James Stadium to face the Tampa Bay Buccaneers. Both teams hold a 4-1 record, making this game significant for their standings. The game will be played on Sunday, October 12, at 4:25 PM, and will air on CBS. The weather forecast predicts a warm day with clear skies and a light breeze, ideal conditions for an outdoor game.

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The 49ers, led by head coach Kyle Shanahan, have shown strength on the road with a 3-0 record away from home. Their offense is guided by Klay Kubiak, while Robert Saleh manages the defense. The Buccaneers, under head coach Todd Bowles, have a 1-1 home record this season. Offensive coordinator Josh Gizzard and defensive coordinators Kacy Rodgers and Larry Foote will look to leverage their home-field advantage. The teams have met frequently, with the 49ers winning the last three encounters.

49ers vs Buccaneers Key Information

• Sport: Football
• Teams: San Francisco 49ers vs. Tampa Bay Buccaneers
• Venue: Raymond James Stadium, Tampa Bay, FL
• Date: Sunday, October 12, 2025
• Betting Odds: 49ers Moneyline +134, Buccaneers Moneyline -159, 49ers Spread +3.0 (-112), Buccaneers Spread -3.0 (-108), Total Over 47.5 (-109), Total Under 47.5 (-111)

Buccaneers vs 49ers – NFL Week 6 Betting Preview

The Tampa Bay Buccaneers return home riding Baker Mayfield’s MVP-caliber start, while the San Francisco 49ers continue to juggle injuries across their offense.

Both teams sit at 4-1, but the paths couldn’t be more different — Tampa Bay has won four nail-biters by a combined nine points, while San Francisco’s depth has been tested weekly. With Brock Purdy likely sidelined and Mac Jones nursing multiple injuries, the 49ers’ offensive continuity will be the biggest question entering Sunday.

The Buccaneers can win if

Baker Mayfield continues his precision passing and connection with rookie receiver Emeka Egbuka. Mayfield ranks top five in the league in both passing yards (1,283) and touchdown passes (10), throwing just one interception in 172 attempts.

With Mike Evans (hamstring) still out, Egbuka has exploded as a reliable WR1, catching 25 passes for 445 yards and five touchdowns. His speed and route discipline give Tampa an edge against a 49ers secondary missing multiple starters.

Defensively, Tampa Bay must maintain pressure up front. The Buccaneers have 15 sacks this season, and forcing Mac Jones off-platform could expose his limited mobility due to knee and oblique injuries.

If Mayfield keeps the tempo high and the defense prevents chunk plays from San Francisco’s backups, Tampa Bay could make another statement win at home.

The 49ers can win if

Their defense creates turnovers and Mac Jones can stay upright. San Francisco’s pass rush — even without Robert Beal Jr. and Yetur Gross-Matos — remains potent, and Kyle Shanahan’s schemes can still generate open looks for Kendrick Bourne and the short passing game.

Bourne, coming off a career-high 142 yards against the Rams, has chemistry with Jones dating back to their time with the Patriots. If Jones can manage the pain and get rhythm early with Bourne, San Francisco can sustain drives and keep Mayfield off the field.

The 49ers’ run game, led by Elijah Mitchell and Jordan Mason, also needs to shoulder the load with Purdy out. If they can establish early success, San Francisco could grind down Tampa Bay’s defensive front and control time of possession.

Line Movement and Odds

Opening: Buccaneers -2.5 / 49ers +2.5
Current: Buccaneers -3.5 / 49ers +3.5
Total: 43.0 points

The line jumped to -3.5 with Brock Purdy expected out. Tampa Bay is 4-1 ATS this season, while San Francisco is 1-3 ATS in its past four games as a road underdog.

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Matchup Breakdown

Tampa Bay ranks eighth in scoring (27.4 PPG) and top five in red-zone conversion rate. Mayfield’s accuracy and decision-making have kept Todd Bowles’ offense balanced despite missing key weapons.

San Francisco remains top-10 in total defense but has been hit hard by injuries. The 49ers’ road wins have come by razor-thin margins (average of 4.6 points). Without Purdy, their offensive ceiling drops considerably.

For detailed performance splits, check the NFL teams page or the Expert Betting Guide.

Injury Report

Tampa Bay Buccaneers

• WR Mike Evans (hamstring) – out
• WR Chris Godwin Jr. (fibula) – questionable
• RB Bucky Irving (foot/shoulder) – doubtful
• CB Zyon McCollum (thumb) – questionable
• CB Benjamin Morrison (hamstring) – out

San Francisco 49ers

• QB Brock Purdy (toe) – out
• QB Mac Jones (knee/oblique) – limited, probable
• WR Jauan Jennings (ankle/rib) – out
• WR Ricky Pearsall (knee) – doubtful
• DE Robert Beal Jr. (ankle) – out
• DT Alfred Collins (knee) – out

Weather in Tampa: 84°F, light humidity, minimal wind — favorable for passing.

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Prop Spotlight

Baker Mayfield Over 1.5 Passing TDs (-125)
Mayfield has thrown multiple touchdowns in four straight games and faces a 49ers defense that has allowed 7 passing scores over the last three weeks.

Emeka Egbuka Anytime Touchdown (+130)
Egbuka leads all rookies in TD catches and has found the end zone in three consecutive games.

Best Bets and Prediction

San Francisco’s injury list keeps growing, and Tampa Bay’s offense has become one of the league’s most efficient behind Mayfield’s poise and Egbuka’s emergence. The 49ers’ travel, health, and quarterback uncertainty tilt the advantage strongly toward the home team.

Prediction: Buccaneers 27, 49ers 20
Best Bet: Buccaneers -3.5 (-110)
Secondary Lean: Over 43 (-110)

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