The 49ers announced on Monday that Garoppolo underwent an MRI Monday morning that determined he suffered a torn left ACL.
That will end Garoppolo's season after just three games.
Head coach Kyle Shanahan is expected to address the injury Monday afternoon.
Garoppolo, who signed a five-year, $137.5 million deal with the team in March, was injured in the fourth quarter of Sunday's 38-27 loss to the Kansas City Chiefs.
Garoppolo scrambled from the pocket and headed toward the left sideline. He grabbed his left knee as he fell to the ground along the sideline.
"We're fearing ACL," Shanahan told the media after the game
Backup quarterback C.J. Beathard will become the team's starter for the remainder of the season. He started five games for the 49ers last season, and the team went 1-4 in those starts. In the seven games he played in 2017, Beathard completed 54.9 percent of his passes with four touchdown passes and six interceptions.
He did not attempt any passes after replacing Garoppolo on Sunday.
Garoppolo was 20-of-30 for 251 yards with two touchdowns on Sunday, and he passed for 718 yards with five touchdowns and three interceptions this season.
"Obviously, I feel for him, personally," Shanahan said Sunday. "I know how disappointed he is. I haven't had a chance to see him yet, but I feel for him."