Machado's fifth-inning blast erased a 4-3 deficit for the Orioles, who took three of four games against the Angels.
J.J. Hardy also contributed a two-run homer and Ryan Flaherty capped the scoring with a two-run single as Baltimore notched a fourth win in six contests overall.
Jason Hammel (5-1) racked up his third win in three starts despite yielding four runs on nine hits over six innings.
Angels starter Jerome Williams (1-1) was tagged for five runs on four hits in a 4 1/3-inning effort.
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