Brian Bruney pitched a hitless eighth, and Mariano Rivera struck out two in around an infield hit for his first save of the year.
Fifty-six of Rivera's 483 saves have come in Pettitte wins.
Only one ball was hit out of the infield by either team after Mark Teahen's inning-ending flyout in the sixth. With two outs in the ninth, Teahen got the Royals' fourth hit on a slow-roller to first.
Derek Jeter had an RBI grounder and Nick Swisher doubled home a run for the Yankees. Mike Jacobs singled home the Royals' run in the second.
New York evened its record at 2-2 following a pair of opening losses at Baltimore and a series-finale win at Camden Yards. The Yankees are on a nine-game trip before opening their new ballpark.
Sidney Ponson (0-1), who made 15 starts for New York last year, gave up four runs and six hits in his Royals' debut. He was signed by Kansas City on March 17.
A capacity crowd of 38,098 crammed into what is virtually a new ballpark, with wraparound seating, wider concourses, outfield party decks, a team hall of fame and a barbecue restaurant. Festivities marking the reopening of the stadium and the start of the Royals' 40th season delayed the start for 32 minutes.
Ponson got in trouble in the first when Johnny Damon singled, Mark Teixeira walked and Posada lined a two-run single past Jacobs at first .
After retiring the first five batters, Pettitte walked Billy Butler and then Jacobs lifted a high fly ball into shallow right-center. Swisher appeared to lose the ball in the sun and it glanced off his glove, a play ruled an RBI double.
Swisher doubled in the fourth and scored when Jeter hit into a forceout.
After giving up a leadoff double to Mark Teixeira in the fifth, Ponson struck out Hideki Matsui, Posada and Swisher around a walk to Robinson Cano, all on called third strikes.
Kyle Farnsworth was booed during pregame ceremonies after giving up the game-losing, three-run homer to Jim Thome of the Chicago White Sox in Tuesday's opener. He entered in the seventh and struck out the side.
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