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.
2014: The Year in Music [PHOTOS]