Jim Thome hit a solo home run in the fourth inning, his first since coming to Baltimore from Philadelphia after the start of the season. He has 610 home runs in his 22-year career, moving him past Sammy Sosa into seventh place on the all-time list.
The Orioles built an 8-1 lead through four innings while winning their third straight.
Miguel Gonzalez (2-1), making his third major league start, gave up two runs on seven hits in 6 2/3 to get the win.
Baltimore roughed up Derek Lowe (8-8) for nine runs on seven hits and five walks in only three-plus innings.
The Indians have lost five out of seven.