With the scored tied 1-1 in the ninth, Jonathan Broxton (3-2) induced Josh Harrison to line out to begin the frame but McCutchen followed by slicing a 1-1 pitch into the right-center field stands for the game-winner.
The blast handed a victory to Joel Hanrahan (5-1), who walked two batters but held the Reds scoreless in the top of the ninth.
Pirates starter Kyle McPherson tossed six frames of shutout ball and Alex Presley provided an RBI double as Pittsburgh evened its three-game series.
Scott Rolen's run-scoring single in the eighth had forged a 1-1 tie for the National League Central champion Reds.
Cincinnati starter Mike Leake blanked the Bucs on four hits over six innings.