Lester (8-7) has a winning record for the first time this season. The Red Sox have won two straight and four of six.
After needing 33 pitches to get out of the first inning on a hot, muggy night at Fenway Park, Lester settled down and took a shutout into the sixth. He left with one out in the seventh after striking out six and holding the Twins to one run, four hits and a walk.
Edward Mujica pitched the ninth and earned his second save.
Phil Hughes (7-3) took the loss for the Twins, who have dropped four straight. The Red Sox have held Minnesota to one run and seven hits in the first two games of the series.
Hughes gave up two runs and eight hits in eight innings and struck out six.
Holt started in center field, his sixth position of this season, and made a sensational catch in left when Jonny Gomes lost a pop fly in the lights. Holt came from nowhere and made a diving catch to end the inning.
He received an ovation during his entire trot to the dugout and several high-fives and pats on the back from teammates. Holt led off the inning with a double off the Green Monster, stole third and scored on a sacrifice fly to put the Red Sox up 2-0.
After Danny Santana opened the game with a single,, Lester retired 13 of the next 14 batters and didn't allow another hit until Kurt Suzuki singled with one out in the fifth.
Minnesota cut it to 2-1 in the sixth when Santana led off with a double, moved to third on a bunt by Brian Dozier, and scored on Joe Mauer's double.
Dustin Pedroia nearly broke open the game on a fly ball to left that was inches short of a two-run homer. Instead, it was a single, and Pedroia was caught in a rundown. The play was reviewed for several minutes, and the call on the field stood.
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