If nothing else, Penny had established a recent track record of keeping the Red Sox in just about every game he pitched, limiting the opponent to three or fewer earned runs in 11 of his past 13 starts.
But Saturday was one of those days Penny didn't have his good stuff, and the Jays made the big right-hander pay the price.
"It happens," said Penny, who is 6-4 with a 5.02 ERA. "You pitch enough, it's going to happen. Hopefully, it happens a lot more. That means I've pitched for a long time."
With the defeat, the Red Sox saw their American League East lead over the Yankees sliced to two games.
Penny was hardly the only reason for the loss. It wasn't a very productive day for the Red Sox's offense, either, as the Boston bats were the victims in the first Major League win for Jays left-hander Marc Rzepczynski.
Over six innings, Rzepcynski scattered four hits and one run, walking four and striking out four.
"I think he was kind of effectively wild," said Red Sox third baseman Mike Lowell. "He didn't really miss over the middle. We were looking at his starts before and he's a lot more efficient around the zone, but he pitched well enough. He scattered just a few hits and never had any real damage."
There were a couple of positive developments for Boston. For starters, shortstop Jed Lowrie made his return from the disabled list. Not only did Lowrie start for the Red Sox for the first time since April 11, he marked his comeback from left wrist surgery by belting a solo homer over the wall in left in the seventh.
"I feel comfortable," said Lowrie. "I got a good pitch to hit and put a good swing on it. [My first] at-bat, I feel like I wasn't ready to hit, but after that, I felt good."
Boston also got a strong relief performance from Justin Masterson. Inconsistent in the first half, Masterson fired two perfect innings in his first outing following the All-Star break.
"I just went out and pounded the zone and felt real comfortable," said Masterson. "I think a lot of it is just approach, and mentally making sure that your stuff is there on every pitch."
Though they were playing from behind most of the day, the Red Sox did forge in front first. Jason Bay led off the second with a double to left, and Lowell followed with a walk. Rocco Baldelli ripped an RBI single to right, making it 1-0.
"You don't want to go out there and give them a lead like that, especially when we get the 1-0 lead," said Penny. "I've got to go shut them down."
The Jays loaded the bases with nobody out in the second, but managed just one run, and that came on a double-play grounder off the bat of Kevin Millar.
But in the fourth, they started to have their way with Penny. Alex Rios banged out an RBI single to left to give Toronto its first lead. A passed ball by George Kottaras pushed runners to second and third with one out. With two outs, up stepped Jose Bautista, who roped a two-run double to center to make it 4-1.
"The pitch that killed me was the hanging curveball with two outs," said Penny.
Instead of settling down, Penny got right back into trouble in the fifth. Marco Scutaro led off with a double to right, and Adam Lind unloaded for a line-drive homer to left, his 20th on the season.
"We're in a game where we're not able to do much offensively," said Red Sox manager Terry Francona. "We had chances, had runners. We just couldn't do much with it. When they spread it out, it made it a lot tougher for us."