"Nothing was really working," Lester said. "I was rushing through my delivery, not a good tempo. When I did get the groundballs that I needed, they weren't at people. It just wasn't my day. Basically, everything you don't want to do, I did today."
Lester (12-5) had won nine of his past 10 decisions and lasted at least seven innings in eight consecutive starts, but he was knocked out after 2 1/3 innings this time -- the shortest start of his career. The lefty matched a career high by allowing seven earned runs. He gave up eight hits and walked two.
"Today he just seemed a little flat, up in the zone," Red Sox manager Terry Francona said. "He made some mistakes and, on top of that, it seemed like every ball found a hole."
Wells got the Blue Jays rolling in the first with a two-run drive off the facing of the second deck in left.
"It was probably the best pitch I threw all day," Lester said. "It was the only ball that was down. He did a good job of hitting it."
Wells came in 0-for-11 but went 4-for-5 with three RBIs and scored four times to back Jesse Litsch's strong outing. He added a solo shot in the fifth for his team-leading 12th homer.
It was Wells' first multihomer game this season and the 17th of his career.
"I was so bad yesterday," Wells said. "It couldn't go anywhere but up."
A three-time Gold Glove winner, Wells also made a pair of fine catches, both on drives by Jason Bay. Wells ended the third by racing back to the warning track to make an over-the-shoulder, bobbling catch, trapping the ball in his arm. In the sixth, he ranged into deep left-center to deny Bay again with a running catch by the wall.
A broken wrist and a strained hamstring sidelined Wells for 52 games this season, the first of a seven-year, $126 million contract.
Litsch (9-7) pitched six sharp innings to win for the first time since June 26. He allowed three hits, walked three and struck out four.
"They scored runs for him early and he filled up the strike zone, which is what you're supposed to do when you have a lead," Boston's Jed Lowrie said.
Litsch was demoted to Triple-A on July 24 and made three minor league starts before returning Aug. 14 and pitching seven shutout innings at Detroit.
Toronto has won seven of 10 against Boston this season, with eight meetings remaining.
"A lot of the time, especially at this time of the year, it's not always who has the best team, it's who's playing well at the time," Bay said. "Those guys are playing very, very well right now."
Leading 2-0 after Wells' first-inning homer, Toronto made it 3-0 on Jose Bautista's sacrifice fly in the second and then chased Lester in a four-run third.
Wells and Adam Lind singled, with both runners advancing on shortstop Alex Cora's throwing error. Rod Barajas hit an RBI grounder before Lyle Overbay and Kevin Mench followed with run-scoring doubles. John McDonald's single ended Lester's day before Scutaro capped the inning with a sacrifice fly off Chris Smith.
The Blue Jays touched up Smith again in the fourth, when Overbay lined a two-run single off the glove of first baseman Kevin Youkilis.
Smith was replaced by Mike Timlin after Scutaro and Wells homered in the fifth. It was Timlin's 1,050th appearance, tying Kent Tekulve for seventh place on the career list.
"It's kind of cool that it was here in Toronto, where I started, where I had number one," said the 42-year-old Timlin, who broke in with the Blue Jays in 1991.
Boston RHP Josh Beckett (arm numbness) skipped a bullpen session and will not make his next scheduled start, Tuesday at Yankee Stadium. Francona said Beckett will throw in the bullpen Tuesday and probably won't pitch again until Friday. ... Boston knuckleballer Tim Wakefield, out since Aug. 7 with tightness behind his right shoulder, is expected to come off the disabled list Tuesday and start in Beckett's spot. ... Red Sox RF J.D. Drew (back) missed his fifth straight game. "He's pretty sore," Francona said. ... Red Sox SS Julio Lugo, on the DL with a quadriceps injury, will return to Boston on Sunday and have an MRI on Monday. ... RHP David Aardsma (groin) also was headed to Boston for an MRI on Monday and will be placed on the 15-day disabled list Sunday. RHP David Pauley will be called up from Triple-A Pawtucket to replace Aardsma on the roster. ... Toronto demoted struggling RHP Shaun Marcum to Triple-A Syracuse and recalled LHP John Parrish from its top farm club. Parrish will start Thursday at Tampa Bay.