With their loss to the Seattle Seahawks in Week 15 of the 2014–15 season, the 49ers were mathematically eliminated from the postseason, exacerbating tensions between head coach Jim Harbaugh and general manager Trent Baalke.

In the 49ers' first game with new head coach Jim Tomsula, the 49ers defeated the Minnesota Vikings 20–3 on Monday Night Football.

The highlight for the 49ers was Kaepernick hitting wide receiver Torrey Smith for a 75-yard touchdown pass in the fourth quarter.

The Steelers defense had a field day on Kaepernick, sacking him 5 times and making him lose a fumble.

49ers quarterback Colin Kaepernick became the first player since 1925 to throw two interceptions returned for touchdowns (pick sixes) to start a game.

Despite a good showing by the 49ers defense (holding the Packers to a season-low 17 points and sacking Aaron Rodgers 3 times), the 49ers offense struggled all game.

In the second quarter, Colin Kaepernick threw a 76-yard pass to ex-Raven Torrey Smith to extend San Francisco's lead to 13–3.

Much like last year's Thanksgiving Day matchup, the 49ers were unable to stop the defending NFC Champion Seattle Seahawks.

Colin Kaepernick struggled all game long and he was sacked six times, much like Week 4 against Green Bay, where the 49ers were also only held to a field goal.

The 49ers were also without tight end Vernon Davis, who was traded to the Denver Broncos, after nine and a half seasons with the team.

Blaine Gabbert made his second start and remained starter for the rest of the season with Colin Kaepernick undergoing season-ending surgery on his left non-throwing shoulder.

However, the Bears appeared to have the game won when they went down the field after a 74-yard kick return by Deonte Thompson.

But when Robbie Gould came out to attempt a game-winning 36-yard field goal, the kick was wide left, resulting in overtime.

In the overtime period, Gabbert would throw the game-winning 71-yard touchdown pass to Torrey Smith to win the game for San Francisco.

With the loss, the 49ers were eliminated from the playoffs and became the latest Super Bowl host team to fail to play the championship game on its own home field.

Quarterback Blaine Gabbert threw 3 interceptions and receiver Anquan Boldin lost a fumble.