Lester (4-3) allowed two runs — one earned — on six hits and zero walks, striking out nine for his fifth career complete game.
Adrian Beltre also homered and Victor Martinez had three doubles for Boston, which completed a two-game sweep. The Twins have scored six runs total while losing their last three games to fall out of sole possession of first place and into a tie with Detroit atop the AL Central.
Francisco Liriano, who won his first four decisions to start the season, has now lost three straight starts. Liriano (4-3) left after giving up back-to-back doubles to Martinez and Youkilis with two outs in the fifth; the Twins left-hander allowed five runs on five hits and three walks, striking out six.
Lester faced the minimum 12 batters in the first four innings and took a shutout into the eighth, when Michael Cuddyer led off with a double, moved up on a groundout and scored on Delmon Young's sacrifice fly to make it 6-1. The Twins scored an unearned run in the ninth after second baseman Dustin Pedroia botched a double-play ball.
Liriano went 3-0 with a 0.93 ERA in April. But he has allowed 16 earned runs in 23 2/3 innings in May — an ERA of 6.08 — and has lost his last three starts.
Liriano, who hadn't allowed a homer in 50 1/3 innings dating to last season, gave up Beltre's solo shot in the second, then got into more trouble when he walked Pedroia with two outs in the third.
Martinez followed with a double, then Youkilis homered to center to make it 4-1.
Beltre reached base three times, doubling in the sixth and scoring on Joe Mauer's passed ball.
Notes
OF Jacoby Ellsbury (rib) appeared in a rehab game for Double-A Portland, going 3-for-4 with a double, a run and a stolen base. OF Mike Cameron (abdomen) went 1-for-4 with a double, a run and an RBI for the SeaDogs. … The Red Sox designated LHP Scott Schoeneweis for assignment and called up SS Angel Sanchez from Triple-A Pawtucket. … Boston manager Terry Francona said it was a good day to give DH David Ortiz a day off against the lefty Liriano. … ABC News correspondent Bob Woodruff, who was nearly killed by a roadside bomb in Iraq in 2006, threw out the ceremonial first pitch as part of the Run to Home Base program, which helps local veterans dealing with post-traumatic stress disorder. … Justin Morneau hit his 200th career double.