The Reds carried a 9-5 lead into the ninth, but All-Star closer Aroldis Chapman walked four straight batters before he was replaced by J.J. Hoover. Pinch-hitter Wilin Rosario then hit a sacrifice fly to trim Cincinnati's lead to two.
After Charlie Blackmon flied out, Stubbs drove a 1-0 pitch from Hoover (1-9) into the seats in left for his 12th homer. It was Stubbs' third career game-ending homer and first with the Rockies.
Rex Brothers (4-5) picked up the victory despite allowing a pair of runs in the top of the ninth.