Austin Jackson tripled to lead off the top of the sixth and was brought home on a single by Prince Fielder, after Miguel Cabrera was intentionally walked, to score the first run of the game and give the Tigers a 1-0 lead.
Cabrera later scored on a single from Delmon Young to give the Tigers a 2-0 lead.
Pettitte walked the next batter, Jhonny Peralta, to load the bases before recording two straight outs to end the inning. Pettitte has given up seven hits, two earned runs and recorded four strikeouts through six innings.
After allowing seven base runners through the first three innings, Tigers starter Doug Fister settled down in fourth and fifth inning and retired six straight batters.
The Yankees loaded the bases for the third time in game in the bottom of the sixth inning, after Fister gave up back-to-back hits to Mark Teixeira and Raul Ibanez and walked Nick Swisher. But again, New York failed to score, after Curtis Granderson and Russell Martin each struck out swinging.