Purdy started as the third-string quarterback but took the starting role following injuries to Trey Lance and Jimmy Garoppolo. He won all five regular-season games he started, securing a division title and an NFC Championship Game appearance.

Purdy led the 49ers to a repeat division title and set the franchise's single-season passing yards record. He earned his first Pro Bowl selection and led the league in multiple passing categories.

Purdy became the lowest drafted quarterback to start a Super Bowl, completing 23-of-38 passes for 255 yards and a touchdown in a 25–22 overtime loss to the Kansas City Chiefs.