San Francisco 49ers vs Tampa Bay Buccaneers Prediction, Odds and Picks for Today, 10/12/25

The Mac Jones era will continue on here for the San Francisco 49ers as they take on the Tampa Bay Buccaneers in Week 6. Jones has now gotten himself pretty banged up while filling in for an injured Brock Purdy, but he insists he’s going to be OK to play here. The 49ers better hope so, because the next man up is former UDFA Adrian Martinez, who has never thrown a regular season pass.

The prospect of a hobbled Jones going on the road against a very good (although quite injured themselves) Buccaneers team doesn’t sit right with me, so I’m going with Tampa. Even with all their injuries, the Bucs still just managed to beat a really solid Seahawks team on the road last week. And that was despite Sam Darnold lighting it up. Tampa isn’t getting enough respect for being 4-1 with their only loss on the year being in a close game to the defending champion Eagles. The 49ers are also 4-1, but their wins aren’t as impressive, and tellingly, all 4 of them have come by 5 points or fewer.

I’m not giving them too much credit for beating the Saints by 5 or the Cardinals by 1. San Francisco’s defense has looked really shaky, including in their one signature win of the season last week when they beat the Rams. Despite squeaking past Los Angeles in OT, they gave alarmingly gave up 389 yards and 3 touchdowns to Matthew Stafford. The week before that, they gave up 26 in an ugly home loss to Jacksonville. Christian McCaffrey is averaging an abysmal 3.1 yards per carry this year, and top 49ers wideouts Jauan Jennings and Ricky Pearsall are both dealing with injuries. Give me the Bucs minus the points here.

49ers vs Buccaneers best bet: Tampa Bay Buccaneers -3 (-110) available at time of publishing. Playable at that number.

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Sure both teams have some injuries on offense, but they each also have shaky defenses that have been torched through the air recently. All the injuries haven’t really slowed down either offense, as they’re each coming off a relative outburst. At first, the Mike Evans injury looked like it might be devastating for Tampa, but Emeka Egbuka immediately stepped right up as Baker Mayfield’s new favorite target, and the first-round pick from Ohio State already has 5 touchdown catches.

Last week, he shredded Seattle for 163 yards, and should only continue to dominate here at home. The 49ers’ defense is without Nick Bosa for the rest of the year, and they lost a rock in their secondary this offseason when safety Talanoa Hufanga left for Denver in free agency. Perhaps most importantly, not only does Mac Jones not represent much of a downgrade from Brock Purdy at this point, if anything, he’s an upgrade. Jones has thrown just 1 interception through 3 games, while Purdy threw 4 picks in his 2 starts. I see the potential for fireworks here.

49ers vs Bucs prediction: Over 47.5 available at time of publishing. Playable to 48.

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