The Orioles avoided their first four-game sweep in Oakland since Aug. 23-26, 2004, jumping on Anderson (1-1) two days after the A's gave the pitcher a $12.5 million, four-year contract.
Brian Matusz (2-0), like Anderson a hard-throwing lefty, delivered a much-needed morale boost for the struggling Orioles in his first career outing against Oakland. He struck out eight, allowing three runs on eight hits and one walk in 6 1-3 innings.
"Oh, it's huge," Wigginton said of the win. "Hopefully now we can run a streak in the other direction."
Baltimore (2-11) had lost nine in a row since its lone previous victory at Tampa Bay on April 8, and is off to the franchise's worst start since beginning 0-21 in 1988. The Orioles also ended a nine-game losing streak at the Coliseum dating to July 22, 2007.
It doesn't get any easier as the Birds leave the Bay Area, either. The Orioles continue their 10-game trip with three games in Seattle followed by three at Fenway Park against Boston.
Anderson, an 11-game winner in his rookie campaign of 2009, needed only 25 pitches to get through the first two innings. He retired the first eight batters of the game before giving up consecutive two-out singles to Cesar Izturis and Adam Jones and then Wigginton's two-run double.
Nick Markakis followed with an RBI single to make it 3-0, Lou Montanez singled in a run in the fourth and Nolan Reimold hit his two-run double in the fifth.
Wigginton hit a two-run homer with two outs in the ninth off Chad Gaudin.
"We really needed a little boost," Matusz said. "We've been playing good baseball and can't get down on ourselves. We came in today with a lot of fight. We came out swinging and it didn't stop."
Anderson's scoreless streak to start the season ended at 14 innings.
The new deal he received Friday could be worth $31 million over six seasons, with Oakland having club options to keep him for the 2014 and 2015 campaigns. Anderson was too busy to discuss his outing afterward, leaving before talking to reporters and tweeting, "Time to shave and get a haircut!"
Later, after one reporter called him, Anderson said: "It was kind of a perfect storm. I had the scoreless streak going, I just signed the contract, and the Orioles are not off to the best start. I don't know if I was destined for failure or what but it was not my best day."
Anderson's offense couldn't do enough to back him in this one. Jake Fox's RBI single in the fourth got Oakland on the board, then Kevin Kouzmanoff doubled in a run in the sixth and Eric Chavez added a seventh-inning sacrifice fly.
The A's have their first day off Monday, and it's good timing. They host the defending World Series champion New York Yankees for three games starting Tuesday night.
Two relievers who came to Oakland late in spring training, Gaudin and Edwar Ramirez, were with the Yankees last season and are yet to receive their World Series rings.
Perhaps on Tuesday?
"That would be a very classy move if they did," A's manager Bob Geren said.
Oakland's Ryan Sweeney extended his season-opening hitting streak to 13 games with a seventh-inning single. He also made a great catch to rob Justin Turner of an extra-base hit in the ninth.
NOTES: Tejada hopes to be back in the lineup in the next day or two. ... Jim Johnson pitched two innings for his first save after blowing a chance Saturday. ... A's 1B Daric Barton left the game after the fourth with a contusion above his right elbow. Chavez, the regular DH, replaced him for his first appearance on defense this year. SS Cliff Pennington also played for several innings after getting his right hand stepped on. ... A's 2B Mark Ellis, nursing a left hamstring injury that has forced him to miss seven games, could return Tuesday. ... Oakland RHP reliever Michael Wuertz, on the DL with shoulder tendinitis, started a rehab outing for Triple-A Sacramento and allowed two hits with a strikeout and a walk. He likely will make at least one more appearance before he rejoins the A's. ... Markakis has reached base safely in all 13 games this season.