Lester and Hughes each struck out six and both had long stretches of dominance in the game. Red Sox leadoff hitter Brock Holt was the difference, getting two hits and scoring both Boston runs in a tight duel.
Lester (8-7) gave up four hits, one run and one walk in 6 1/3 innings while Hughes (7-3) -- working more economically -- allowed eight hits and two runs without a walk in eight innings.
After Burke Badenhop and Craig Breslow finished the seventh inning for Lester, Junichi Tazawa and Edward Mujica struck out five of the last six Twins batters with Mujica earning his second save of the season.
The Red Sox have won the first two games of the three-game series on the heels of a two-game losing streak while the Twins have now dropped four in a row.
The Red Sox took a 1-0 lead after Holt hit a leadoff single in the first inning, went to second when Eduardo Escobar made a nice play down the third base line and threw Xander Bogaerts out at first, and scored on Dustin Pedroia's double to the left-center field gap.
Holt, in his first game in center field, chased down Brian Dozier's fly ball in deep left-center for a diving catch to end the top of the third inning after left fielder Jonny Gomes appeared to lose the ball in the lights.
Holt then led off the bottom of the third with a double, stole third base and scored on Bogaerts' sacrifice fly to center, giving the Red Sox a 2-0 lead.
Danny Santana's leadoff single in the first inning was Minnesota's only hit until Kurt Suzuki's one-out single in the fifth. In between, Lester retired 11 batters in a row after giving up a two-out walk to Josh Willingham in the first. He struck out the side in the second and stranded Suzuki at first in the fifth.
Santana also had Minnesota's third hit, a leadoff double in the sixth, and later scored on Joe Mauer's lined double to left field.
Hughes kept his pitch count lower than Lester's. The Red Sox ace threw 109 pitches -- 72 for strikes -- before he was relieved with one out in the seventh. Hughes had 94 through seven innings, also throwing 72 for strikes, and finished with 105 pitches (82 strikes).