After pitching had been guiding Baltimore, the club was led by its offense, which matched a season-high with 15 hits in an 8-7, walk-off win.
The Mariners, looking to avoid their first sweep since mid-June, will turn to former Oriole Kevin Millwood to contain Baltimore's offense.
Millwood, who has just one win since May 23 despite a respectable 4.01 ERA, will be facing the Orioles for the first time since 2009.
He's coming off a four-run, six-inning outing against the Yankees, resulting in his ninth loss of the season.
"I thought I located my fastball pretty well and threw some good changeups," Millwood said. "My curveball stunk, but my slider was OK, a little inconsistent. All in all, I had enough to compete and possibly win a game."
The veteran right-hander was a member of the Orioles in 2010, going 4-16 with a 5.10 ERA, but will be facing a much different team than the one he played for two years ago.
Baltimore, which lost 96 games in '10, has been one of the biggest surprises in baseball this season, sitting second in the competitive American League East, just 4 1/2 games behind the Yankees.
Steve Johnson will get the ball for the Orioles on Wednesday, making his first career big league start.
Right-hander Tommy Hunter, who was warming up in the 14th inning of Tuesday's contest after the Orioles burned through seven pitchers, was scratched from the start following the game.
The 24-year-old Johnson has made just one career Major League appearance, throwing two innings for Baltimore last month.
Johnson has appeared in 19 games -- 14 of them starts -- at Triple-A Norfolk this year, going 4-8 with a 2.86 ERA.
Orioles: Wieters finding stroke
All-Star catcher Matt Wieters clubbed two homers on Tuesday -- his first multi-homer game since April -- to give him 15 on the season to go along with 52 RBIs.
After struggling through July, his worst month of the season, Wieters is batting .320 in August with three extra-base hits. He only had four hits go for extra bases in July.
The 26-year-old is well within striking distance of surpassing his career highs in home runs (22) and RBIs (68), both set last season.
Nick Markakis continued his hot-hitting ways at the top of Baltimore's lineup in Tuesday's win.
After going 4-for-7 in the victory, Markakis is batting .360 over 25 games since moving into the leadoff spot for the first time in his career.
Markakis has three homers, 10 RBIs and 19 runs scored over the stretch.
Mariners: Ryan still out
Shortstop Brendan Ryan sat out his third consecutive game Tuesday with an inflamed left elbow.
Ryan has been receiving treatment, but has limited range of motion after getting hit by a pitch from Yankees starter Hiroki Kuroda on Saturday.
The shortstop, who was available as an emergency pinch-runner, is considered day to day.
"They're doing everything they can to get him over it," Mariners manager Eric Wedge said.
Oliver Perez extended his scoreless appearance streak to 11 after blanking the Orioles over two frames on Tuesday.
The lefty has found new life with the Mariners, becoming a dominant reliever after missing all of 2011 following his well-documented struggles with the Mets.
Perez lowered his ERA to 2.08 and has allowed runs in just three of the 20 games he has appeared in this season.
Baltimore is 4-1 against Seattle this year. After Wednesday, the two will meet one more time this season -- a three-game set at Safeco Field in September.