After winning over the Browns, the Steelers traveled further west to take on the Colts in a rematch of 2015's 45-10 blowout win. The Steelers struck first in the first quarter when Le'Veon Bell ran for a 5-yard touchdown to take a 7-0 lead. This would be followed by Ben Roethlisberger finding Antonio Brown on a 25-yard touchdown pass later on in the quarter to make it 14-0. The Colts got on the board in the second quarter when QB Scott Tolzien, starting in place of the injured Andrew Luck, found Donte Moncrief on a 5-yard touchdown pass to make it 14-7. However, the Steelers pulled away as Roethlisberger found Brown again this time on a 33-yard touchdown pass for a 21-7 lead at halftime. After a scoreless third quarter, the Steelers sealed the game with the only points in the second half when Roethlisberger found Brown again this time on a 22-yard touchdown pass and the eventual final score of 28-7. With the win, the Steelers improved to 6-5. Roethlisberger's record as a starter improved to 1-1 on Thanksgiving Day.

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