Baltimore improved to 2-0 with its second straight win over New York.
Uehara, the first Japanese-born pitcher in Orioles history, gave up five hits and a walk before leaving with a 7-1 lead. Signed to a two-year, $10 million contract in January, Uehara (1-0) dominated the Yankees in much the same fashion he ruled for 10 seasons with the Yomiuri Giants.
Asked where this victory ranked in his list of accomplishments, Uehara replied through a translator, "It's right at the top."
It was also a humbling experience for the 34-year-old right-hander.
"The Yankees have a great lineup, a lot of great players," Uehara said. "It was an honor to have a chance to pitch against them and get a win. I'm really grateful and happy."
The Orioles provided Uehara with plenty of offensive support, all of it against Wang (0-1). Making his first start since last June after missing the latter half of the season with a foot injury, Wang yielded seven runs and nine hits in 3 2/3 innings.
"It's been so long, I just wanted to win so bad," Wang, of Taiwan, said through a translator. "Hopefully, I can get my sinker back as soon as possible."
A two-run homer by Derek Jeter got New York to 7-4 in the ninth, and Mark Teixeira greeted George Sherrill with an RBI double to bring the tying run to the plate. Sherrill then retired Hideki Matsui on a popup to earn his first save.
After losing the first two games of the series by a combined 17-10 score, the Yankees -- who own baseball's highest 2009 payroll at $201 million -- will turn to newcomer A.J. Burnett on Thursday to avoid a three-game sweep against a team that last year lost 93 games and finished in the AL East cellar.
"I don't see any panic here," left fielder Johnny Damon said. "But right now, I don't think anybody expected us to be in this situation."
New York's offseason spending spree has yet to provide the desired results. CC Sabathia ($161 million contract) took the loss in the opener, and Teixeira ($180 million) went 1-for-5 Wednesday and is 1-for-9 in two games.
Although the crowd of 22,856 was less than half the Opening Day sellout, most in attendance continued the practice of booing Teixeira during every at-bat because the hometown player spurned the Orioles to sign with New York.
Baltimore sent nine hitters to the plate during a five-run fourth inning that made it 7-1. Gregg Zaun doubled in a run and Cesar Izturis hit an RBI grounder before Adam Jones added a sacrifice fly. Markakis then chased Wang with a two-run homer to right.
It was Wang's shortest start since going 2 2/3 innings against Toronto in August 2007. It was also the first time in nine starts since Sept. 15, 2007, in Boston, that Wang lost on the road.
"He never got his sinker going," Yankees manager Joe Girardi said. "When he doesn't have a sinker, he's going to struggle and that's what happened."
The Orioles used successive doubles by Jones, Markakis and Aubrey Huff to take a 2-0 lead in the first inning. The damage might have been more severe if Huff didn't get caught trying to steal third before Melvin Mora got Baltimore's fourth straight hit, an infield single.
But for the most part, Uehara kept New York off balance by mixing his split-finger fastball with a changeup he learned from Orioles pitching coach Rick Kranitz.
"We didn't hit too many balls off him," Damon said. "His changeup was good and he kept his fastball down. He has a good idea out there."
Matsui went 0-for-3 against countryman Uehara. ... Jones reached base five straight times to open the season before grounding out in the third. ... Wang was 24-5 in his previous 38 starts. ... Yankees starters in two games have yet to record a strikeout.