Masterson (5-7) won for the third time in four starts, yielding a pair of runs (one earned) on five hits without issuing a walk en route to the victory.
The right-hander struck out seven, tossing 65 of his 97 pitches for strikes as the Tribe took three wins in a four-game series at Orioles Park.
Shelley Duncan (3-for-4) smacked a solo homer to put the Indians ahead for good in the second inning and added an RBI double in the fourth, triggering a three-run outburst that put the contest away.
Aaron Cunningham supplied a solo shot for Cleveland.
Baltimore's Brian Matusz (5-10) dropped his fifth straight start, surrendering five runs (four earned) on seven hits over four full innings.
Adam Jones went 2-for-4 with a bases-empty clout for the O's.