Santana (1-6) had lost each of his first six decisions this year and while he had been on the mound in those six starts his teammates had amazingly scored just two runs on his behalf.
Los Angeles ended that stretch Wednesday, producing 14 hits while winning for the fourth time in five games.
Trout had an RBI double during a three-run third and scored on a single from Pujols. Another single by Pujols brought in a run in the fifth and Trout added a run-scoring infield single in the sixth.
Santana allowed two runs on six hits in 7 1/3. One of the hits was a solo homer by Josh Willingham.
Carl Pavano (2-3) surrendered five runs on 10 hits in four-plus innings to suffer the loss.