Kimbrel, the Boston Red Sox closer, blew the save opportunity when he allowed a leadoff homer to Kendrys Morales in the bottom of the ninth to tie the game at 1-1.
When Mookie Betts hit a three-run double in the 10th, the Red Sox went on to defeat the Toronto Blue Jays 4-1 as Kimbrel finished off the bottom of the inning.
Sale struck out 13 in allowing four hits and one walk in four in eight innings.
"He was outstanding," Red Sox manager John Farrell said. "Powerful, a lot of strikes. All three pitches working. He had such good-swing-and-miss to his fastball up and away. Eight dominant innings. Every inning he has pitched this season, his back has been against the wall in some sense where he's had very little margin for error."
So why take the left-hander after only 102 pitches?
"Tough decision," Farrell said. "We felt like it was time to turn to it over to a guy who was fresh and powerful. Unfortunately, the second pitch goes out of the ballpark."
"I threw the first pitch of the game (to Kevin Pillar) and it was almost a homer," Sale said. "You try not to lose focus. Anytime you have something like that going, you try not to get lax. Sometimes you can be striking guys out and the next thing you know, you've got guys on first and second, a three-run dinger and you're sitting on the bench asking yourself what happened."
Toronto's Marco Estrada matched Sale for six innings, allowing three hits and two walks. He had seven strikeouts.
"Those guys just put up good at-bats," Estrada said. "We didn't give up too many hits today but they fouled off a lot of good pitches. It's frustrating, sometimes you make a good pitch and they foul it off instead of popping it up or grounding out or whatever. They did a good job over there, that's why I only lasted six innings."
"Estrada was very good," Farrell said. "Just a dynamite changeup, good location."
"It was a good, tight, well-pitched ball game on both sides," Blue Jays manager John Gibbons said. "Any time Sale is pitching, he's a high strikeout guy anyway, and when he's on, there's really not a whole lot you can do."
The Red Sox (10-6) took the rubber match of the three-game series with the Blue Jays (3-12).
The Red Sox took a 1-0 lead in the top of the ninth.
Roberto Osuna gave up a two-out double to right-center to Mitch Moreland, and Xander Bogaerts followed with a single down the right-field line to score the Moreland. Right fielder Jose Bautista threw out Bogaerts at second as he tried for a double.
Morales tied the game when he led off the bottom of the ninth with a homer, his third of the season.
Jason Grilli (0-2) walked Sandy Leon with one out in the 10th inning, and Brock Holt singled him to second. Marco Hernandez ran for Leon. Dustin Pedroia fouled out to third, and Andrew Benintendi walked to load the bases. Betts cleared the bases with a double to left.
"The based are loaded, you don't have a lot of wiggle room in those situations," Grilli said. "I tried to come in on him. He's a good hitter, he got his hands in on it and did what he could. Tip your hat to him."
"I was just trying to put a good swing on a good pitch," Betts said. "(Sale) did what he's been doing his whole career. When somebody goes out and pitches eight innings like that, you have to try to get them a win some way."
The Blue Jays' struggles have them looking for answers.
"It would be understandable if we were on a different team with different names on that team," Estrada said. "You look at the names we have here, you start thinking how is it happening with a lineup like that and the staff that we have, a good bullpen and everything.
"It's weird. It's hard to explain right now. I feel like we have been playing better of late. I think things are going to turn around. It almost feels like the first few weeks were a fluke, it shouldn't be happening with a team like this."
NOTES: Boston OF Mookie Betts struck out in the fourth inning Wednesday to end a streak of 129 consecutive regular-season plate appearances without a strikeout dating to Sept. 12, spanning 29 games. It was the longest streak in the majors since OF Juan Pierre went 147 plate appearances without a strikeout in 2004. Betts struck out in his first two plate appearances Thursday. ...Toronto CF Kevin Pillar singled in the eighth to extend his hit streak to eight games. ...Toronto opens a four-game series against the Los Angeles Angels Friday with RHP Mat Latos (season debut) called up from Triple-A Buffalo to start against Angels RHP Alex Meyer (season debut). ...The Blue Jays will recall RHP Casey Lawrence from Buffalo to start Saturday against the Angels. ...The Red Sox will start LHP Drew Pomeranz (1-0, 5.23 ERA) Friday in Baltimore against Orioles RHP Dylan Bundy (2-1, 1.86 ERA) in the opener of a three-game series.