The White Sox, who came in with a 1 1/2-game lead on the Minnesota Twins in the AL Central, lost their second straight.
Coming off a 6-3 road trip and with Josh Beckett placed on the disabled list, Boston used Matsuzaka (16-2) in his place against the AL Central leaders. He pitched one of his most efficient games of a season in which he's been among the AL ERA leads while giving up the most walks in the AL.
He struck out seven, walked two and threw 104 pitches. The only hits he allowed were singles by Jermaine Dye in the second and Alexei Ramirez in the third. His 16 wins tied Hideo Nomo's single-season record for the most by a native of Japan.
Bay's three-run double in the sixth put Boston ahead 7-0 and gave him 27 RBIs in 25 games since a three-way trade on July 31 that brought him from Pittsburgh and sent Manny Ramirez to the Los Angeles Dodgers.
Pedroia scored three runs, giving him 104 for the season and breaking Bobby Doerr's record for Boston second basemen of 103 set in 1950.
The Red Sox took a 1-0 lead in the first off Javier Vazquez (10-12) when they loaded the bases with no outs on a walk and two singles then scored when Kevin Youkilis hit into a forceout at second base.
They made it 3-0 in the fifth when Pedroia singled, stole second and scored on David Ortiz's double. Ortiz took third on a single by Youkilis and scored on a double by Mark Kotsay, playing his first game at Fenway since being acquired from Atlanta on Wednesday.
The Red Sox added four runs in the sixth with a huge assist from Chicago catcher A.J. Pierzynski.
He dropped leadoff hitter Alex Cora's foul pop behind home plate for an error and Cora capitalized with a double. Had Pierzynski caught it, Vazquez might have gotten out of the inning quickly because he retired the next two batters.
Instead, Cora took third on a wild pitch and Pedroia walked. Horacio Ramirez then walked Ortiz, loading the bases. D.J Carrasco came in and got ahead of Youkilis with a 1-2 count but hit him with the next pitch, forcing in a run.
Bay, who struck out three times Friday, then hit his bases-clearing double off the left-center field wall that just eluded center fielder Nick Swisher.
The Red Sox made it 8-0 in the eighth when Pedroia led off with a single, took second on Ortiz's single and scored on Youkilis' double.
Notes:@Boston CF Coco Crisp was scratched from the lineup with flu-like symptoms. ... The Red Sox placed Beckett and 1B Sean Casey on the 15-day disabled list and purchased the contract of C David Ross from Triple-A Pawtucket. ... Chicago lost its second straight game after winning three in a row.
