Lester (9-6) yielded a second-inning homer to Wil Myers but then settled down, blanking the Rays over the next three innings on his way to breaking a personal three-start losing streak.
The left-hander ended up allowing two runs on seven hits and didn't issue a walk for the Red Sox, who rebounded from a 3-0 loss in Monday's four-game series opener and moved 1 1/2 games ahead of Tampa Bay atop the American League East.
Mike Carp's RBI single in the third inning put the Bosox ahead to stay at 2-1, Dustin Pedroia added a sacrifice fly in fifth and Julio Iglesias iced the win with a two-run single in the eighth for Boston.
Roberto Hernandez (5-11) took the loss, yielding three runs on seven hits over five full frames.
Evan Longoria went deep for the Rays, who lost for only the third time in 21 games.