The Padres held a 1-0 lead for much of the game until the Rockies finally broke through for a run in the top of the eighth against Luke Gregerson (6-7) on a RBI single from DJ LeMahieu.
But Gyorko responded quickly, leading off the next half-inning by knocking a pitch from Matt Belisle (5-6) 358 feet over the fence in right field.
Tyson Ross fired seven innings of shutout ball, scattering three hits and a pair of walks while striking out five for San Diego, which clinched its three-game series.
Huston Street wrapped up the win with his 28th save.
Rockies starter Tyler Chatwood yielded just one run on five hits over six innings.
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