This time, however, the two All-Stars had misfires that proved costly in a tough 5-4 loss to the Astros on Monday in Game 4 -- which wound up being the elimination game for the Red Sox.
The Red Sox had taken a 3-2 lead in the fifth on Andrew Benintendi's two-run homer to right against Justin Verlander and the Fenway crowd was starting to believe there would be a Game 5 in Houston on Wednesday.
Sale created excitement when he came out of the bullpen in the fourth inning, his team down by a run at the time. He threw one nasty pitch after another for his first four innings, striking out six
When Sale came out for the eighth, he was at 65 pitches and pitching on three days' rest following his loss in Game 1 in Houston.
"Very comfortable," Red Sox manager John Farrell said of Sale coming back out for the eighth. "We're in a position with six outs to go, up a run, and Chris Sale who was still strong, still throwing the ball extremely well. I felt like we were in a good position."
But that position was no longer as good when Alex Bregman belted the fourth pitch of the inning, a 2-1 changeup, over the Green Monster for a stunning game-tying solo shot.
It was stunning because Sale had been in such control before that. It was Bregman's second home run of the series off Sale, as the Astros' third baseman also took him deep in the first inning of Game 1.
"I felt good, I felt strong. I wish I could have got it done," said Sale. "Changeup. I tried to get him out in front. Didn't work."
There was still hope for the Red Sox because they still had Kimbrel. He came on for Sale with pinch-runner Cameron Maybin on first and two outs, and the dangerous top of the order coming up for the Astros.
Kimbrel's first high-leverage appearance of the series started ominously, as he walked George Springer. The righty was one strike away from getting out of the eighth with the game still tied, but Josh Reddick placed his 99.3-mph fastball past the shortstop hole and into left for the go-ahead RBI single.
"I came in, had guys on, I wanted to get out of it," said Kimbrel. "Had a good battle against Reddick. He hit the ball where nobody was, scored a run. I felt like we had momentum going our way. It's a tough way for it to end, unfortunately. We have a good group of guys in here. We fought hard. It's tough to come up short at the end of the day."
In the ninth, Kimbrel again faltered, giving up an RBI double to Carlos Beltran in what proved to be a pivotal insurance run.
"Any time [Kimbrel] steps on the mound, you have all the confidence in the world," said Sale. "He's one of the best to ever step out there. Obviously you never want to come out, but handing it over to him makes it a little easier."
Sale's first season in Boston resulted in his first career postseason appearance, but the end was bitter.
"It's tough," Sale said. "We come here to win. We worked hard. It came down to the wire, it was a close game. This one definitely stinks."
Ian Browne has covered the Red Sox for MLB.com since 2002. Follow him on Twitter @IanMBrowne and Facebook. This story was not subject to the approval of Major League Baseball or its clubs.