Lackey (5-5) held the Rockies to two runs on eight hits over seven innings. The veteran right-hander didn't issue a walk in firing 73-of-98 pitches for strikes.
Junichi Tazawa pitched a scoreless eighth inning and Koji Uehara, newly anointed as Boston's closer, tossed a 1-2-3 ninth for his second save as the American League East-leading Red Sox won both ends of a two-game interleague set.
Shane Victorino went 3-for-4 with an RBI and two runs scored while Daniel Nava drove in a pair of runs for Boston.
Rockies starter Roy Oswalt (0-2) was tagged for five runs on nine hits over six full frames.
Michael Cuddyer belted a pair of solo homers in the loss, Colorado's seventh in nine games.