It was his 213th victory as Yankee, putting him third on the franchise's career list behind Whitey Ford (236) and Red Ruffing (231).
Pettitte (5-3) had six strikeouts and no walks in his 85-pitch effort. He has 1,940 strikeouts as a Yankee, 16 behind franchise leader Ford.
Pettitte is 12-13 in 26 career starts against the Mariners, the only American League team he has a losing record against.
David Robinson worked out of a jam in the eighth and Mariano Rivera took over in the ninth, earning his 630th career save, adding to his major league record.
Rivera has 22 saves in 23 opportunities this season and is 36 of 38 for his career against the Mariners.
Jayson Nix had a pair of RBI singles and Brett Gardner had three hits, including two doubles.
The Yankees scored a two-out run off Joe Saunders (4-6) in the first inning. After Mark Teixeira doubled down the left-field line, Robinson Cano drove him home with a single to right for his 40th RBI.
Jason Bay opened with a single to left in the Mariners' fourth, the first baserunner Pettitte allowed. Kyle Seager followed with a first-pitch single to right, extending his hitting streak to 12 games.
Kendrys Morales then bounced a potential double-play grounder to shortstop Nix. He bobbled it and was late to tag second. He still threw to first for the out.
Michael Morse then hit a sac-fly to center, scoring Bay.
The Mariners' failure to turn a double play in the fifth allowed the Yankees to jump ahead, 2-1. Ichiro Suzuki walked and advanced to second on Chris Stewart's one-out single to center.
Gardner then hit a one-hopper to third baseman Seager. He threw quickly to second for the force but second baseman Nick Franklin bobbled the relay and Gardner reached.
Nix then drove Suzuki home with a single to right.
Nix also drove home the final run in the seventh on a single to center, scoring Gardner, who had doubled.
Kevin Youkilis entered the game tied with Boston's David Ortiz for reaching base safely in all 20 games they have started at Safeco Field. His sixth-inning walk gave him 21 straight.
NOTES: Yankee RHP Michael Pineda, who had labrum surgery 14 months ago, began his rehab assignment with Single-A Tampa Saturday. His recovery has been slow but Yankee manager Joe Girardi said that's expected "because shoulders and elbows are precious." . LHP Vidal Nuno was removed from his start for Triple-A Scranton/Wilkes Barre Friday because of a groin injury. Girardi said that generally means a trip to the DL. . The Mariners placed C Jesus Sucre on the DL, retroactive to June 6, with a left wrist sprain. SS Carlos Triunfel was recalled. . C Brandon Bantz, who was a backup Double-A catcher a week ago, made his first big league start. "There's no story bigger," Mariners manager Eric Wedge said. "It means everything. It's not a job; it's a dream. . good for him." . Morales was removed in the sixth with back stiffness. He is day to day. . The Mariners drafted the younger brother of 3B Seager, Justin Seager, in the 12th round Saturday. He is a first baseman for North Carolina-Charlotte.