The Rockies overcame two home runs and three RBI from Chase Headley to win their second in a row.
Colorado's big second inning also featured a two-run double by Chris Nelson and Michael Cuddyer contributed a two-run shot in the fifth that boosted the Rockies' lead to 7-1.
Juan Nicasio (1-0) lasted 6 1/3 innings to get the win, allowing four runs on seven hits. San Diego starter Clayton Richard (1-1) surrendered eight runs on 10 hits in 5 1/3.
San Diego has lost six out of seven. Colorado completed a nine-game homestand with a 5-4 mark.