Upton, who had an MRI earlier this week after complaining of right knee discomfort and missed his second straight game Friday, will receive a platelet-rich plasma injection and will need six weeks of recovery. He is expected to be ready for spring training in 2020.
It was an injury-plagued season for Upton, who went on the injured list in late March because of turf toe on his left foot and missed the Angels' first 71 games. Limited to 63 games, he finished with just 12 homers and 40 RBIs, his lowest totals since his 43-game rookie season in 2007.
Trout missed his fifth straight game Friday with an irritated nerve in his right foot. He was in the Angels' early lineup but was scratched about two hours before game time to give him another day of rest. The Angels aren't expected to shut down Trout, who leads the American League with 45 homers.
Ohtani had surgery Friday on his left kneecap and will need eight to 12 weeks of recovery.
The Angels were mathematically eliminated from postseason contention with Tuesday's 8-0 loss to the Cleveland Indians.
Information from The Associated Press was used in this report.