His arm dangling, a stunned Lackey walked off the mound with two outs in the bottom of the fifth with a right biceps strain.
The severity of the injury was not immediately known, and Lackey will undergo an MRI in Boston on Sunday.
"He felt kind of a cramping sensation," said manager John Farrell. "Obviously we took him out immediately, but once he was in the clubhouse here, he iced it down. That cramping went away. The strength test, at least in the training room, showed to be positive, in terms of full strength. We're going to get him back and get a full exam likely tomorrow."
It was a cruel twist of fate for Lackey, who had spent 18 months on the rehab trail from the surgery he underwent after the 2011 season.
"It was a pretty good cramp. It's all in the biceps. It's not the elbow," said Lackey. "It's frustrating, and it was scary when it happened. It's sore, but hopefully not too serious."
After an incident-free Spring Training, Lackey got off to a good start on Saturday, striking out eight over 4 1/3 innings.
On a 2-2 pitch to Jose Reyes, Lackey immediately started shaking his arm and muttering in pain. He experienced slight discomfort on the previous pitch, flexing his arm a bit.
"I felt a little something tight on the pitch before, but it grabbed me pretty good on the last pitch," Lackey said.
The way Lackey pitched early on, it's hard to believe things would transpire the way they did. The righty had six strikeouts through the first three innings.
The Jays finally did something against him in the fourth when J.P. Arencibia drilled a two-run homer, making it a 2-0 game.
"He looked sharp," said Farrell. "He had good action to his secondary stuff. The velocity was probably the best we've seen to date. He was free and easy. He threw all his pitches for strikes. He gets a cutter up in the zone to Arencibia and we are well aware of what he can do with a pitch up in the strike zone."
A two-run deficit seemed bigger to the Red Sox on a day they did nothing offensively against Jays lefty J.A. Happ and a collection of Toronto relievers.
"He was throwing strikes, he was mixing in his changeup, he had a really good changeup today," said Arencibia. "He had a good slider, a good breaking ball and he was able to throw to both sides of the plate, and I think he really commanded his secondary stuff, which made his fastball that much better."
Jacoby Ellsbury doubled to lead off the game. Aside from that, the Boston bats were handcuffed the entire afternoon and didn't generate their next hit until Dustin Pedroia had an infield single with two outs in the ninth.
"Well, J.A. Happ did a good job of staying out of the middle of the plate," said Farrell. "Fastball, changeup, he's got deception. Swing and miss to his fastball. We saw it a number of times today. He used his changeup in key spots in the 3-2 count to Pedroia, for one, to get the popup. You couldn't sit on any one pitch in a given area. We had the one opportunity where he walked the guys in the one inning, but he made some pitches to get out of any jams."
Alfredo Aceves, who came on for Lackey, gave up a three-run homer to Colby Rasmus in the bottom of the sixth.
It could be Aceves who pitches in Lackey's next scheduled turn in the rotation, but the Red Sox aren't ready to make any decisions like that just yet.
"We've got to get through tomorrow and then factor everything in that we do get information from," said Farrell.