Pettitte allowed three hits and struck out seven over eight innings to give the Yankees a solid start against a team that won a record-equaling 116 games during the regular season. Seattle beat New York in six of their nine meetings during the regular campaign.
A member of the Yankees' rotation since 1995, Pettitte has been a key component of New York's four World Series titles in the last five years.
"I just had good stuff today," Pettitte said. "I really felt like I had a good curveball, a better curveball than I've had in a while. I was really able to throw it for strikes whenever I wanted to. I was able just to move my fastball around a little bit, and then, you know, the big key to when I have success is getting some double plays, and I was able to do that today."
Pettitte (1-1) improved to 9-5 lifetime in the postseason. In two playoff starts this season, he has allowed two runs and 10 hits in 14 1/3 innings.
"He's confident in what he does," O'Neill said. "He knows that if he makes his pitches, he's going to get people out, and that's good to see. He doesn't second-guess himself."
It was the fourth straight win in the playoffs for the Yankees, who faced elimination three times against the Oakland Athletics in the division round and survived each contest.
Pettitte outpitched Seattle starter Aaron Sele, facing the minimum number of batters in all but one inning.
Sele had to work his way out of trouble in the first inning, but the Yankees touched him for the first run of the series in the second.
Jorge Posada reached on a leadoff walk and was still there two outs later. But Alfonso Soriano singled Posada to second and Chuck Knoblauch hit a sharp grounder down the third base line and the ball glanced off the glove of a diving David Bell.
As Bell scrambled for the ball in foul territory, Posada came around to score.
The Yankees increased their lead in the fourth on the key blow of the contest. Posada led off the inning with a double and O'Neill drove him home with a low liner to right that sailed into the seats.
O'Neill, who has been a staple in the middle of the Yankees' lineup over the last nine years, has been bothered by a stress fracture in his left foot.
"I'm sure if you asked Sele, he made a mistake. He got a pitch up," O'Neill said. "That's an easier pitch to pull, obviously. We scored a couple early and our pitching has been phenomenal.
"To score early has been so big. Obviously, when Andy is throwing the way he was, we score some runs, then we've got a good shot."
It was O'Neill's first postseason home run since Game 4 of the 1998 ALCS against Cleveland. The 38-year-old O'Neill, who won a World Series under Piniella while with the Cincinnati Reds in 1990, has hinted that this season may be his last.
"He comes up with some big hits," Yankees shortstop Derek Jeter said. "That was a big hit for us today. Anytime you can get a home run in the postseason it is important, because runs are hard to come by. He had a big game today."
"Paul is dangerous," Seattle manager Lou Piniella said. "He's got all that postseason experience and he's had a heck of a career. We were supposed to throw him a nice sinker down and away there but the ball just stayed up over the middle of the plate and he hit it out."
Seattle got one run back in the fifth, but wasted a chance for another one. Edgar Martinez opened the inning with a single and went to third on a double by Mike Cameron. John Olerud's ground out to shortstop allowed Martinez to score and sent Cameron to third, but he was stranded there when Pettitte struck out both Jay Buhner and Dan Wilson.
New York added an insurance run in the ninth against reliever Jose Paniagua. Soriano began the inning with a line drive off the left-field wall. Soriano, thinking he had hit a home run, failed to run all out and wound up having to settle for a single.
But the speedy Soriano eventually stole second and scored on a two-out single by David Justice.
Mariano Rivera came on in the ninth to record the 22nd playoff save of his career, but not without giving up a double to Ichiro Suzuki, two wild pitches that brought Suzuki around to score and a walk to Bret Boone that brought the tying run to the plate.
But Edgar Martinez grounded out to first base to end the game.
Sele, who was tagged in Game 3 of the division round against Cleveland, survived six innings. He allowed three runs and seven hits with three walks and three strikeouts.