Luck marched the Colts down the field with time running out, connecting with Wayne four times on the drive -- including a four-yard TD toss with 35 seconds remaining.
Mason Crosby missed a 51-yard field goal try for Green Bay with 8 seconds left, securing the victory for the Colts (2-2).
Luck finished 31-of-55 through the air for 362 yards, two touchdown and an interception, while Wayne made 13 grabs for 212 yards in the win.
Colts head Coach Chuck Pagano missed the game after being hospitalized to undergo leukemia treatment. Team owner Jim Irsay intended to deliver him the game ball from the triumph, ESPN reported.
Rodgers completed 21-of-33 passes for 243 yards, three touchdowns and a pick-off while also rushing five times for 57 yards for the Packers (2-3).