Sale struck out 12 in seven dominating innings, and Devers hit a game-tying homer off Chapman's 103 mph fastball as the Red Sox edged the Yankees 3-2 on Andrew Benintendi's bases-loaded single in the 10th.
While Sale's 16th double-digit strikeout game and Benintendi's hit off Tommy Kahnle helped the Red Sox win for the 10th time in 11 games and take a season-high 5 1/2-game lead on the Yankees, it was Devers' swing that left everyone abuzz, especially considering who it occurred against and how rare a feat it was.
"An incredible swing," Boston manager John Farrell said.
Devers hit the 1-2 pitch over the 399-foot sign into the Boston bullpen beyond the left-field wall. It was the left-handed-hitting third baseman's fourth homer in 15 career games.
"First time," said Devers through an interpreter when asked if he ever saw a 103 mph pitch. "I've seen 100, but never 103."
Said Sale, who was in the training room watching the game on television on a delay: "You can't help but smile."
It also was the first homer hit by a left-handed hitter off Chapman since Luke Scott had one June 26, 2011, for the Baltimore Orioles against the Cincinnati Reds. For Chapman, it was the second time a left-handed hitter homered off him in his career, which has seen him faced 444 left-handed hitters in 379 at-bats in the regular season and postseason.
"To me, it was a good pitch, a good fastball," Chapman said through an interpreter. "He made contact."
Yankees manager Joe Girardi said of Devers, "We know the young man has power, and if you put the barrel of the bat to a 100 mile per hour fastball, it's probably going to go somewhere."
Chapman (4-2) blew a save for the fourth time in 10 attempts, and it was the fourth time in six appearances against the Red Sox he was scored upon. He was charged with the winning run as Benintendi singled after Chapman hit Jackie Bradley Jr. and walked Eduardo Nunez.
Before Devers homered, the Yankees took a 2-1 lead in the eighth on a bases-loaded sacrifice fly by Todd Frazier off Matt Barnes. In the bottom of the ninth, the Yankees missed a chance to win it when Brett Gardner struck out with Chase Headley on third against Craig Kimbrel (4-0).
Before Boston's rookies helped the Red Sox beat the Yankees for the first time in a game Sale pitched, their ace allowed one run on four hits and two walks during his 51st career double-digit strikeout game.
He hit 99 mph on the final pitch of his 114-pitch outing, but the Red Sox did little offensively, costing Sale a chance at becoming the American League's first 15-game winner.
Sale upped his major-league-leading strikeout total to 241. He also became the first pitcher to record three straight double-digit strikeout games against the Yankees since Pedro Martinez in 2001, according to STATS.
"Tonight, he was hitting his spots," Yankees right fielder Aaron Judge said. "He was making pitches when he had to. He just didn't make a mistake."
Before Sale's night ended and the Yankees went ahead in the eighth, both teams scored in the fifth.
Bradley Jr. hit an RBI single off New York starter Jordan Montgomery, and Austin Romine hit a run-scoring triple off Sale.
Montgomery made the start in place of the injured CC Sabathia (knee), even though he was hit in the head during batting practice Saturday. He allowed one run and two hits in 5 1/3 innings.
The Red Sox (67-50) made several hard outs in the opening four innings against Montgomery, including a diving catch by center fielder Aaron Hicks on Eduardo Nunez's liner to start the game.
Boston broke through with two outs in the fifth inning. Brock Holt walked, took second on a wild pitch and scored standing up on Bradley's single to left field just under shortstop Didi Gregorius' glove.
The Yankees (61-55) tied the score in the bottom of the inning. Headley hit a one-out single. With two outs, Romine lifted an 0-2 slider to deep right field. The ball caromed off Mookie Betts' glove, and Romine reached third with his first career triple.
NOTES: Boston LHP David Price (left elbow inflammation) threw for the third straight day. He will get a scheduled day off Monday before resuming Tuesday. ... 1B Greg Bird (bruised right ankle) will start a rehab assignment Wednesday, and 2B Starlin Castro (strained right hamstring) will start a rehab assignment Friday, though the Yankees did not say which minor league affiliates they would play for. ... Red Sox RHP Carson Smith (recovery from Tommy John surgery) made his third rehab appearance for Triple-A Pawtucket on Saturday, and Boston manager John Farrell said Smith's velocity was increased and the command was good. Smith will make his next appearance Tuesday.