Pujols and Callaspo each had four hits while Josh Hamilton contributed a two-run homer as the Angels romped in the opener of a four-game series.
Los Angeles sent 11 men to the plate during a seven-run sixth inning that broke the game open.
Jason Vargas (6-4) held the Mariners to two runs on four hits over seven innings to earn the victory.
M's starter Aaron Harang (3-7) was lit up for 12 hits over five innings, yielding four runs.
Nick Franklin belted a two-run homer for Seattle.