"It's hard for me to fathom that a guy can record that many strikeouts in less than 1,300 innings," Red Sox manager John Farrell said. "Really remarkable."
Even Sale (15-6), who struck out 11 and allowed three hits in seven innings, considered his achievement "pretty crazy."
"This game has been around a long time," he said. "To do that, it's cool. I appreciate it. I try not to get too caught up in it but I definitely take a step back and look at that and appreciate it."
Sale's milestone, a called third strike for his third strikeout of the game, came in 1,290 innings pitched.
Former Chicago Cubs ace Kerry Wood held the previous record, reaching 1,500 in 1,300 innings pitched.
Sale, acquired in a blockbuster offseason trade with the Chicago White Sox, entered Tuesday night's game in Toronto with a 14-6 record, 2.88 ERA and an MLB-best 253 strikeouts.
Sale, 28, has been the ace of the Red Sox's pitching staff and a leading candidate for the American League Cy Young Award. But he was coming off his worst start of the season in a 13-6 loss to the Indians, in which he gave up seven runs -- six earned -- in just three innings pitched.
Farrell credited his ace for "an outstanding effort."
"That was a vintage Chris Sale outing," he said. "He was powerful, he threw a lot of strikes."
Information from the Associated Press was used in reporting.