Machado delivered a run-scoring double in the fifth, snapping a 1-1 tie, and added a three-run blast in the sixth to break the contest open.
Chris Davis provided a solo shot for the Orioles, who clinched their three-game inter-league series.
Wei-Yin Chen (1-2) earned the victory, allowing one run on three hits over six innings. The left-hander overcame four walks and struck out two.
Tommy Hunter picked up his first career save with three innings of scoreless relief for the Orioles, who took Saturday's first game 7-5.
Dodgers starter Josh Beckett (0-3) remained winless after surrendering six runs on eight hits over 5 2/3 innings.
Adrian Gonzalez drove in the Dodgers' run.