Pinch-hitter Michael Cuddyer collected a single off Brett Myers (0-2) with one out in the 10th, and Fowler then lashed a pitch down the line past diving first baseman Carlos Lee to the right-field corner.
Brian Bogusevic retrieved the ball and fired it in but a sliding Cuddyer just beat the relay to the plate for the game-winning score.
Fowler finished 4-for-4 with a solo homer, three RBI and three runs scored while Marco Scutaro added a bases-clearing double for the Rockies, who had beaten the Astros 9-7 in the opener.
Josh Roenicke (1-0) earned the win with a scoreless top of the 10th.
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