After his start was pushed back two days, Lester matched his season high with eight strikeouts and overcame homers by Wil Myers and Evan Longoria as the Red Sox won 6-2 on Tuesday night and moved 1 1/2 games ahead of the Rays in the AL East.
This game was more important than some others for Lester, who had struggled after a sensational opening month.
"You never want to diminish any start," Boston manager John Farrell said, "but, again, where we are in the standings, where they are (and) knowing we're only still in July, but this was a big game for us."
The win kept the Red Sox (61-41) atop the division for the 58th consecutive day and moved them within eight victories of their total from last season.
"Anytime you play somebody in your division, it's more than just a regular-season game," Lester said, "whether it be the first part of the year or last part of the year. It's always big to beat somebody in your division, whether they're half a game back or 20. It doesn't matter. If you continually beat the people in your division, you're going to have a good season."
Lester (9-6) had been scheduled to make his first start after the All-Star break on Sunday. But that was delayed for two days to give him nine days of rest.
"He was strong," Farrell said. "It seems like the added rest did him some good."
The loss ended the Rays' six-game winning streak and was just their third in 21 games, a surge that began when they were in fourth place, trailing the Red Sox by seven games.
"We've been playing pretty darned good and I am not going to be negative or critical about our group at all. We got outpitched a little bit," Tampa Bay manager Joe Maddon said. "Lester was a strike-thrower tonight."
Boston is 3-4 since its four-game winning streak.
Lester gave up two runs and seven hits with no walks in 6 1-3 innings. He is 3-6 with a 5.97 ERA since starting the season 6-0 with a 2.72 ERA. Four Red Sox pitchers combined for 13 strikeouts.
Roberto Hernandez (5-11) allowed three runs in five innings and tied R.A. Dickey for the second-most losses in the AL. But it was the 28th time in Tampa Bay's last 31 games that its starter gave up three runs or fewer.
"He kept us in the game and gave us a solid chance to win," Maddon said.
Boston led 3-2 before scoring three runs in the eighth on an RBI single by Stephen Drew and a two-run single by Jose Iglesias.
Myers' fifth homer of the season on the first pitch of the second inning cleared the left-field wall and gave the Rays a 1-0 lead.
"That was pretty cool, especially to be able to hit it over The Monster," Myers said. "I got a good pitch and just ended up taking advantage of it."
The Red Sox tied it in the bottom half on a run-scoring single by Mike Carp.
They went ahead 2-1 in the third on a double steal. Shane Victorino led off with a double and went to third on a flyout by Daniel Nava. Dustin Pedroia was hit by a pitch and then stole second as catcher Jose Molina threw down and Victorino scored.
The Red Sox had left runners at third base in three straight innings before Pedroia gave them a 3-1 lead with a sacrifice fly in the fifth.
The Rays got another leadoff homer off Lester in the sixth when Longoria hit his 21st on the second pitch, cutting the lead to 3-2.
"Those leadoff home runs like that can turn into big innings if you let them," Lester said. "I was able to settle back down and get some outs after that."
And the Red Sox remained in first place.
"It was a very big performance" by Lester, Victorino said. "You needed something like that, especially (against) a team that's been playing very well."
NOTES: Myers missed the previous two games with a sore left wrist. He is 16 for 32 in his last eight games. ... Rays 1B James Loney's single in the second was the 1,000th hit of his career. ... Pedroia was the only Red Sox batter who went hitless. ... Boston is 10-4 against Tampa Bay and has clinched the 19-game season series. The last time the Red Sox won the season series over the Rays was 2007. ... Alex Torres pitched two scoreless innings and has allowed one run in 30 1-3 innings for the Rays. ... David Price (4-5) pitches for the Rays against Felix Doubront (7-3) in the third game of the four-game series. ... Rays RHP Alex Cobb threw only two pitches in his first rehab start for Class-A Charlotte against Dunedin. Cobb, sidelined since he was hit in the head by a line drive, was removed as a precaution due to a blister on his right index finger. ... Boston CF Jacoby Ellsbury got the night off. He leads the majors with a .370 batting average since May 26.