Pujols put the Angels ahead to stay with a first-inning sacrifice fly, added a run-scoring single in the next frame and then popped a two-run homer in the sixth as Los Angeles clinched its three-game set at Coors Field.
Mike Trout knocked in a pair on three hits with a trio of runs scored, while Torii Hunter also scored three times, going 3-for-4 for the Angels. Howie Kendrick and Alberto Callaspo chipped in three hits each.
Dan Haren (4-6) notched the win despite allowing four runs on 10 hits over 5 1/3 innings.
Jeff Francis (0-1), making his first start for Colorado this season after a year-long stint in the minors, was rocked for eight runs on 10 hits in a 3 1/3-inning start.