Following a rain delay of 2 hours, 4 minutes, Gonzalez hit an RBI double and scored on Will Middlebrook's two-run double in the first, then hit a three-run homer off CC Sabathia in the fifth.
Chris Stewart's first home run since September cut the gap to 3-1 in the third, but Gonzalez boosted the lead with two outs in the fifth when he lined a home run into the right-field bleachers. Gonzalez leads the majors in batting average with runners in scoring position at .418 (41 for 98).
New Yankees right fielder Ichiro Suzuki raced into the right-center gap to rob Gonzalez of an extra-base hit with a catch just in front of the warning track in the seventh.
Lester, who had been 0-3 with a 10.42 ERA in his previous four starts, allowed four runs and four hits in six innings and watched his bullpen blow a lead he left with for the fifth time. He fanned Robinson Cano in the sixth for his 1,000th strikeout.
"We needed to win that game," Lester said. "Guys came back and kept fighting. That was big for us."
NOTES: Valentine caused a stir before the game when he said the Red Sox medical staff instructed him not to play LF Carl Crawford four days in a row, a mandate Valentine said he ignored earlier in the month after the left fielder came off the DL. ... Former Red Sox manager Terry Francona visited with Boston players before the game in the Red Sox clubhouse, preparing for his job as a broadcaster for Sunday night's game on ESPN. ... Sabathia gave up a season-high six runs and eight hits in six innings.