Lackey (1-1), who had been shelved since suffering a right bicep strain April 6, tamed the Astros on one run over six innings. The right-hander allowed five hits, walked two and struck out four.
David Ortiz went 2-for-4 with a pair of RBI, collecting his 16th and 17th hits in the eight days since his April 20 season debut.
Stephen Drew added a two-run triple and Daniel Nava went 2-for-4 with three runs scored for Boston, which improved to a major league-best 18-7.
Astros starter Bud Norris (3-3) yielded five runs (three earned) on nine hits over six full innings.
Ronny Cedeno drove in Houston's only run.