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.
McPhee, Cokas 'working on their marriage' after affair
Ohio bar shooting arrested, charged with murder