It was a rare setback for the A's, who fell to 18-4 this month and 12-3 since the All-Star break. The Athletics need to win one of their next two games to complete the best July in franchise history.
Chen (9-6) allowed one unearned run, three hits and four walks in 5 2/3 innings against a torrid Oakland team that had scored 40 runs in its previous four games.
Alternating an accurate fastball with a sharp-breaking curve, the left-hander struck out every A's starter except No. 9 hitter Brandon Hicks.
"When he has stuff like that today, he's going to get some strikeouts," said Wieters, Chen's battery mate. "More importantly, their team was trying to be patient and wait him out, and that's going to get you in some deeper counts. When he got the two strikes, he was able to put them away."
Chen, who pitched four seasons in Japan before coming to Baltimore, set a major league record for strikeouts by a Taiwanese-born pitcher. The old mark was 10 by Chien-Ming Wang in 2007.
"I'm sure he'll be modest about it, but there's not a second you don't take that in and realize (what it means)," Orioles manager Buck Showalter said. "When you talk about the history of baseball, it always gets my attention. It was fun to watch. I don't for a second not take in what it means to the people of Taiwan. I'm sure they're very proud of Wei-Yin, probably as much as we are."
The strikeouts mean less to him than getting deeper in the game. He threw 108 pitches and didn't get out of the sixth.
"I really (need to) lower my pitch count to win the game," Chen said.
The last time an Orioles pitcher had as many as 12 strikeouts was in July 2007, when Erik Bedard fanned 15 against Texas. Chen also became the first Oriole to get at least 10 strikeouts in fewer than six innings.
In two starts against Oakland this year, Chen is 2-0 with an 0.71 ERA.
"Well, he was really good. We've seen him twice and he's been good against us twice," Oakland manager Bob Melvin said. "Today, he was just throwing his fastball by us. He wasn't afraid to use it. He was throwing it to both sides of the plate and using breaking balls to keep us off-balance."
A's starter Travis Blackley (3-3) gave up five runs, six hits and four walks in five innings. He was 3-0 in six starts since June 10.
Omar Quintanilla had three hits, including a homer, to help Baltimore win for only the second time in seven games.
"Chen came out and he did his thing. He threw real well, and overall it was a great team effort," Quintanilla said. "We've just got to keep it up."
Lew Ford, whose contract was purchased from Triple-A Norfolk before the game, went 0 for 3 with a walk in his first big league game since 2007. But the Orioles left fielder contributed a strong throw to cut down Yoenis Cespedes, who was trying to stretch a second-inning hit into a double.
After going 0 for 6 with runners in scoring position in a 6-0 loss Saturday night, the Orioles got two such hits in a four-run fourth. With runners at first and second and one out, Adam Jones doubled in a run. Wieters then ended a 1-for-31 skid with a drive into the left-field seats, only the third homer allowed by Blackley in 67 innings this season.
Limited to one hit through five innings, the A's finally got to Chen in the sixth. Jemile Weeks walked and Jonny Gomes reached on an error by Quintanilla at second base before Cespedes hit an RBI single. After a single by Brandon Inge loaded the bases, Darren O'Day retired Derek Norris on a popup.
Orioles 2B Brian Roberts announced before the game that he will undergo season-ending surgery to repair a torn labrum in his right hip. Roberts, 34, played in only 17 games this season. ... Oakland obtained C George Kottaras from the Milwaukee Brewers in a trade for minor league reliever Fautino De Los Santos. ... A's OF Coco Crisp missed the game with a tight left hamstring, but RF Josh Reddick returned after missing one game with a bruised back. ... Oakland opens a 10-game homestand Monday at home against Tampa Bay. The A's are 8-2 during a stretch of 17 straight games against the AL East. Baltimore travels to Yankee Stadium for a three-game series that starts Monday night.