Joe Saunders (2-3) allowed a pair of runs in his 105-pitch effort, giving up four hits and a walk while striking out two.
Michael Saunders, meanwhile, socked a solo homer in the first inning and added an RBI on a fielder's choice during a three-run sixth as the Mariners notched a third straight win.
Jason Bay went 3-for-4 with a run-scoring double while Kyle Seager added two hits with an RBI in the victory.
Orioles starter Zach Britton (0-1) was roughed up for six runs on 10 hits over six full frames.
Matt Wieters belted a two-run homer as Baltimore dropped the first of a three-game series.