Hunter Pence belted the game-winning home run in the eighth inning to lift Houston to a 4-3 win over New York in the second installment of a four-game set.
Pence hit two home runs and drove in all four runs for the Astros, who have won four out of five.
Mark Melancon (1-0) earned his first major-league win despite giving up the game-tying home run in the top of the eighth and Wilton Lopez worked a scoreless ninth to earn his first big league save.
Johan Santana (10-7) took the loss in a complete-game effort, his second straight, allowing nine hits while walking one and striking out seven for the Mets, who have dropped three out of four.
David Wright's lead off long ball to left knotted the game at three in the eighth. It was his first run batted in during the month of August.
Pence then hit his game-winner to left on a 3-2 pitch with one out in the home half.
Jose Reyes opened the game with an infield hit, moved to second base on a wild pitch and scored the game's first run on a base hit by Fernando Martinez.
The Astros responded with three in their half of the frame on Pence's home run to left field. Michael Bourn and Angel Sanchez had singled ahead of the long ball to start the frame.
The visitors answered with a run in the second on an RBI ground out by Reyes that plated Josh Thole, who had started the inning with an infield hit and moved to third on a Santana double.
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