Tillman (1-0), recalled from Class AAA Norfolk Tuesday, gave up only a pair of unearned runs while striking out seven and walking two.
The right-hander tossed 79 of his 125 pitches for strikes and Jim Johnson nailed down his 25th save as the Orioles took the rubber match of a three-game series.
Adam Jones socked a solo homer while Robert Andino went 2-for-3 with an RBI single for Baltimore.
Seattle starter Hector Noesi (2-11) remained winless since May 6, a span of 10 starts. The right-hander surrendered four runs on seven hits in a five-inning effort.
Justin Smoak and Kyle Seager each drove in a run for the Mariners.