"An outstanding night tonight again from Clay," Red Sox manager John Farrell said. "He was in command and control the entire seven innings."
Stephen Drew hit a two-run shot in the second inning and Napoli went back-to-back with Daniel Nava in the fourth as the Red Sox won their majors-best 19th game and improved to 8-3 away from home, the best road record in the big leagues.
The Red Sox have hit 16 home runs in five games at Rogers Centre this season. That's one more than they've hit in their other 22 games combined.
"When the roof is closed and it's warm in here, the ball definitely flies," Farrell said. "We've got guys that obviously can hit some good fly balls that carry here. This is a very good hitter's ballpark and we were able to put some good swings on pitches."
Napoli hit a solo shot into the second deck in center in the fourth and followed up with a three-run shot into the third deck in the seventh. Napoli, who also doubled in the ninth, has six home runs this season and leads the majors with 21 extra-base hits.
"Impressive, to say the least," Farrell said.
Buchholz (6-0) allowed two hits, walked three and struck out eight, improving to 7-0 in his past eight starts at Toronto. The right-hander lowered his ERA to an AL-best 1.01. Only St. Louis Cardinals right-hander Jake Westbrook (0.98) is better.
"Overall I felt really good with everything today," Buchholz said.
Buchholz is off to the best beginning to a season by a Red Sox pitcher since Josh Beckett opened 7-0 in his first seven starts of 2007. He said his curveball was the best it's been all season.
"Today it definitely had a little bit more bite to it, it was a little bit more sharp," Buchholz said.
Boston catcher David Ross, however, thought the two-seam fastball was Buchholz's best pitch.
"A lot of those guys knew what was coming and still couldn't hit it," Ross said. "As far as how he can execute four to five pitches on both sides of the plate, there's not many other guys like that in the big leagues. That's why he's doing what he's doing."
The Blue Jays didn't get a runner past first base until Adam Lind walked and went to third on Melky Cabrera's single in the seventh. But Cabrera was thrown out trying to stretch his hit into a double before J.P. Arencibia struck out to end the inning.
"Buchholz just never gave us anything," Blue Jays manager John Gibbons lamented.
After rallying to beat the Red Sox 9-7 in Tuesday's series opener, the last-place Blue Jays couldn't maintain any momentum, losing for the seventh time in nine games. Toronto has won consecutive games just once this season, April 12 and 13 at Kansas City.
Blue Jays left-hander Mark Buehrle (1-2) surrendered three home runs for the second straight start and has allowed nine home runs in six starts this season. Buehrle gave up five runs and seven hits in 6 2/3 innings. He walked a season-high three and struck out one.
Three of Boston's first five outs were fly balls to the warning track. After Middlebrooks was hit by a pitch in the second, Drew made sure he cleared the wall by homering into the second deck in right, his first.
Napoli led off the fourth with a drive to center, his fifth, and Nava followed with a shot to left, his fifth. It was the fourth time this season the Red Sox have hit consecutive homers, and the second time they've done it against Toronto.
Boston chased Buehrle and broke the game open with a four-run seventh, doing all its damage with two outs. Esmil Rogers came on after a two-out walk to Jonny Gomes, who went to third on Dustin Pedroia's single and scored on a wild pitch. Ortiz was intentionally walked before Napoli clubbed his second home run of the night. For Napoli, it was the 11th multihomer game of his career and his first this season.
"The game was still manageable going into the seventh inning there and then it exploded on us," Gibbons said.
Ortiz went 1 for 3 and has hit safely in all 10 games since coming off the disabled list.
"David's presence can't be understated in any way," Farrell said.
Brett Lawrie drove in Toronto's only run with an RBI triple off Wilson in the eighth.
Blue Jays RHP R.A. Dickey has been diagnosed with mild inflammation in his neck and back following an MRI, and will get an extra day of rest before his next start, Saturday against Seattle. RHP Josh Johnson, who was scratched from his start last Friday with tightness in his right triceps, will return to the rotation Friday. ... Boston OF Shane Victorino (back) swung the bat for a second straight day and remains on track to take full batting practice Thursday. Victorino, who has not played since Apr. 24, hopes to return for Friday's game at Texas. Victorino has missed six straight games.