Berken (2-9) allowed three runs and five hits in six innings. The right-hander, who walked two and struck out six, had lost nine straight decisions since beating Romero and the Blue Jays in his major league debut.
"The first [win] obviously came fast," Berken said. "It's been a long two months, that's for sure. It feels good to have a happy interview for a change."
Berken was also grateful the Orioles didn't yank him out of the rotation as his struggles mounted.
"I just knew the opportunity was only going to be there for so long and I needed to start pitching better," Berken said. "Tonight was a step in the right direction."
Despite his successes against Romero and the Jays, Berken is in no rush to face Toronto again anytime soon.
"I'd prefer not to," he said with a smile. "They have some good hitters in that lineup. If I could stay away from them, that would be good."
Trailing 7-3, Toronto cut the deficit in half against right-hander Chris Ray in the eighth. Vernon Wells hit an RBI single and Alex Rios added a sacrifice fly, with both runs charged to Matt Albers. Ray ended the rally by getting Edwin Encarnacion to ground out.
Jim Johnson worked the ninth for his third save as the Orioles won for just the sixth time in 21 games since the All-Star break.
"I thought tonight [Berken] grew up and the guys really rallied behind him," Orioles manager Dave Trembley said. "I'm happy for him, I'm happy for the team. It's been a real, real tough stretch, obviously."
Toronto (51-57) lost its third straight and dropped a season-high six games below .500.
Hit hard in his last start, when he allowed six runs and seven hits in just 1 1/3 innings against Boston on Aug. 2, Berken faced more early trouble Friday when Wells and Rios hit back-to-back homers in the second. Wells' homer was his 11th, while Rios' was his 13th. It's the fourth time this season Toronto has hit consecutive homers.
"He could have caved in and the team could have as well," Trembley said. "It could have been 'Here we go again.' He didn't do it."
Berken set down nine of the next 10 batters before the Blue Jays struck again in the fifth. Aaron Hill doubled just beyond the reach of Reimold in left, scoring Joe Inglett, but Berken retired five more in order before giving way for Albers.
Romero (10-5) lost for just the second time in 11 starts. He allowed four runs and four hits in six innings, walked two and struck out three.
"I felt like I made some good pitches, got ahead of hitters but just couldn't put them away when I had to," Romero said.
Bidding for his fourth straight win, Romero mowed down the first nine batters before Brian Roberts walked to begin the fourth. Roberts went to third on two groundouts but was thrown out at the plate when a pitch bounced away from catcher Rod Barajas.
Baltimore erased Toronto's lead with a four-run fourth. With the bases loaded, Markakis hit a two-run double that bounced off the glove of first baseman Lyle Overbay. Aubrey Huff followed with an RBI single and Reimold capped it with a run-scoring grounder.
The Orioles pulled away with a three-run seventh against Brandon League. Reimold hit an RBI single and left for pinch-runner Felix Pie, who scored on a base hit by Ty Wigginton. Matt Wieters followed with an RBI double.
The Blue Jays honored 35 players and coaches from their 1992 and 1993 World Series championship teams who were on hand for a weekend reunion. The attendees were introduced before the game, with manager Cito Gaston throwing out the first pitch to Pat Borders, MVP of the '92 World Series victory over Atlanta. ... Baltimore traded C Gregg Zaun to Tampa Bay for cash or a player to be named and promoted C Chad Moeller from Triple-A Norfolk. ... The Orioles won a series opener for the first time in 11 series. They last did it June 26 against Washington.