The 2018 season was the San Francisco 49ers' 69th in the National Football League (NFL), their 73rd overall, their fifth playing their home games at Levi's Stadium and their second under the head coach/general manager tandem of Kyle Shanahan and John Lynch.

However, the 49ers' season ended with a record of 4–12 and were plagued by multiple season-ending injuries, including running back Jerick McKinnon tearing his ACL in training camp and quarterback Jimmy Garoppolo tearing his ACL in Week 3 against the Kansas City Chiefs.

In Week 15, however, the 49ers upset the Seahawks 26–23 in overtime at home, snapping the 49ers' 10–game losing streak to them that dated back to the 2013 NFC Championship Game.

During the entire 16 game schedule of the 2018 NFL season, the 49ers defense would accumulate just two interceptions, breaking the previous mark of three.

The 49ers entered free agency with the following:[3] Notes Draft trades Front office Head coaches Offensive coaches Special teams coaches Strength and conditioning Running backs (RB) Wide receivers (WR) Tight ends (TE) Defensive linemen (DL) Defensive backs (DB) Special teams Reserve at U.S. Bank Stadium, Minneapolis, Minnesota First quarter Second quarter Third quarter Fourth quarter Top passers Top rushers Top receivers

The next day, an MRI further revealed that Garoppolo had torn his ACL, ruling him out for the rest of the season.

Playing a winless Cardinals team desperately seeking a win, the 49ers held rookie QB Josh Rosen in check, but were hurt by five offensive turnovers, one of which resulted in a defensive touchdown for Arizona.

The 49ers drop to 1–4 (0–2 since Garoppolo's injury) heading into a Monday Night road game against the Packers.

On the 49ers' next drive, a critical C. J. Beathard interception plus an illegal contact penalty on Richard Sherman in the final minute led to a 27-yard game-winning field goal by Mason Crosby to send the 49ers to a 33–30 loss and a 1–5 record heading into next week's home game against the undefeated Rams.

This was the first time since 2013 that the 49ers beat the Seahawks, snapping a 10-game losing streak which dates back to the 2013 NFC Championship Game.

During the season finale against the Rams, Kittle broke Travis Kelce's single-season receiving yards record for a tight end, less than an hour after Kelce broke the record, on a 43-yard touchdown and finished the season with 1,377 yards.