Pettitte (11-11), who announced this month he would end his likely Hall of Fame career after this season, notched his 256th win and his 26th complete game, becoming the only pitcher in major league history with more than 15 years and no losing seasons.
The left-hander walked two and struck out five, helping New York clinch its season-ending, three-game series.
Paul Clemens (4-7) was hung with the loss, surrendering two runs (one earned) on five hits over 5 1/3 innings for the hapless Astros, who dropped a 14th straight.
Chris Carter drove in Houston's run.
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