It will be the second stint this season as the No. 1 quarterback for Winston, who started three games after coming on in relief of Ryan Fitzpatrick in Week 4. However, Winston was benched after a four-interception performance at Cincinnati on Oct. 28, only to replace Fitzpatrick after he stumbled in last week's 38-35 defeat at the New York Giants.
Winston passed for 760 yards with four touchdowns and four interceptions in his first two starts -- a 34-29 loss at Atlanta and a 26-23 home win over Cleveland. He told reporters this week that his only clunker among the three starts was against the Bengals.
"Guys, again, you guys really look at film, the Cincinnati game was just a really bad game," Winston said. "If you were to grade me in those other two games, I played pretty good football. The Atlanta game I had a bonehead turnover in the red zone that could've cost us. The Cleveland game, I had a bonehead turnover in overtime. Previous to that, we drove the ball downfield and we gave our team a chance to win late in the game."
Fitzpatrick guided Tampa Bay to victories in the first two games of the season, eclipsing 400 yards in each while throwing for eight touchdowns against one interception. He also went for 400 yards with three touchdowns and three picks in Week 3 before laying an egg at Chicago in Week 4.
Winston served a three-game suspension to open the season for violating the league's personal conduct policy. The No. 1 overall pick in the 2015 NFL Draft, Winston said he understood why head coach Dirk Koetter went back to Fitzpatrick given his early-season success.
"I think we can go back to how this season started. Fitz-magic. That was all the talk. He was playing excellent," said Winston. "And again, if you watch the film, he was playing good. We made some mistakes. ... I can't control the perception of Fitz-magic. I bought in too because our team was winning."
After Fitzpatrick threw three interceptions and put Tampa Bay in a 31-14 hole against the Giants, Winston came off the bench and led the Buccaneers to touchdown drives on four straight possessions. Winston finished 12-of-16 for 199 yards with two touchdowns and an interception.
"We've talked about this before," Koetter said. "The reason people don't switch quarterbacks in the NFL is because they either don't like their backup or they don't trust their backup. And so, hey, I've had quarterbacks be hot and cold before and we've stuck with them because they were really our only quarterback. You weren't going to put your two in there. That's just not the case this year because of the way the year started."
San Francisco has had its own issues at quarterback. Starter Jimmy Garoppolo suffered a torn ACL in Week 3 and backup C.J. Beathard was knocked out of the lineup with a concussion sustained in Week 8.
That forced the 49ers to start undrafted free agent Nick Mullens in Week 9 and he responded by throwing three touchdown passes and zero interceptions in a 34-3 thrashing of Oakland in his NFL debut. He came back to earth with 250 yards with one touchdown and two picks in a 27-23 loss to the Giants before last week's bye.
"I'm always self-scouting. I have a lot of things I need to work on," Mullens said. "It's always running through your mind. It keeps me pretty angry most of the time, to be honest. I'm always hard on myself. There's definitely some things I need to get better at for this team to be better."
San Francisco head coach Kyle Shanahan is optimistic that wideout Pierre Garcon could return Sunday. Garcon hasn't played since Week 9 against the Raiders. Running back Matt Breida, who has been nicked up all season, figures to be as healthy as he's been in several weeks after the bye week.
"There's a lot on the line," said Shanahan. "You come back and people might think you don't have much to play for. You have everything to play for. You have your career, you have your livelihood, you have the guys next to you and you have showing people that you want to be in this building."