The Indians (24-20) scored a combined six runs between the third and fourth innings, all charged to Sale, and defeated Chicago 6-2 to pull within 1 1/2 games of the White Sox (27-20) for the top spot in the American League Central.
Josh Tomlin (7-0) started for Cleveland and stayed perfect, allowing only two runs in eight innings to out-pitch Sale (9-1), who took his first loss of the season.
"I'm not out there hitting and neither is (Sale), so I'm not facing him at the plate and I'm not the one scoring the runs," Tomlin said. "For me, it was just to go out there and attack them with the same gameplan and keep it as close as I could, because I know who that guy is. He's one of the better pitchers if not the best pitcher in baseball right now. I understand that aspect of it and I understand my job is to keep their runs as minimal as I can."
Tomlin allowed a home run to Adam Eaton on his second pitch of the game, but yielded just one more run for his career-high seventh straight win. He struck out six, walked only one and threw 76 of his 99 pitches for strikes.
"He gets it in there," White Sox manager Robin Ventura said. "(He's) very effective with the cutter. Not a lot of fastballs. Everything just seems to be cutting in (or) running away ... hitting the strike zone too."
Eaton went 2-for-4 with the homer and Jose Abreu went 3-for-4 with two doubles to lead the White Sox (27-20). Abreu came into the game hitting just .100 (2-for-20) in his past five games, but his breakout performance wasn't enough to overcome Sale's tough night.
Sale, who threw 89 pitches in his 3 1/3 innings, was attempting to become the eighth player in major-league history to win his first 10 starts. Andy Hawkins, who did it in 1985, is the most recent player who accomplished the feat and the previous seven all did it before 1920.
Sale finished with seven strikeouts, which moved him past Ted Lyons for sole possession of eighth in White Sox history (1,080), but the loss ended the left-hander's career-high 10-game win streak that stretched back to last season.
Chicago dropped to 3-6 in the first nine games of a 10-game homestand, has lost eight of its past 11 games and 10 of the last 14. Sale, however, put this one squarely on his own shoulders.
"You chalk it up as a bad night," he said. "I'm not going to pinpoint this or that. I stunk. I was bad. I was terrible. Embarrassing, quite honestly. It's tough to go out and go 3 1/3 (innings). It's tough. You leave your team in a tough position, especially after a doubleheader. That's what gets me the most. We played two (Monday). I had to be big for the guys tonight and was the exact opposite."
Trailing 1-0 after Eaton led off the White Sox's first with a home run, the Indians got to Sale for three runs in the third and fourth to lead, 6-1.
The third played the biggest role in Sale's undoing. He allowed three runs on three hits and two walks and threw 43 pitches after retiring the first two hitters on just five pitches. By the time the inning ended, 38 pitches later, Sale had thrown the most pitches in an inning in his major-league career, putting him at 70 to that point.
He threw 19 more in the fourth, including one Gimenez hit for a long lead-off homer. Sale was replaced by right-hander Zach Putnam after allowing two more walks and an RBI single by Lindor.
"We talked before the game about how one of the best ways to get good pitchers, to beat them, is to maybe get them out of the game," Indians manager Terry Francona said. "In the third inning we did a really good job with the pitch count and we scored. And then we followed it up with even more (in the fourth), which was big. We made him work and we'll take a win, because (Sale) is, by far, one of the best in the game."
Sale left the field to a round of applause from White Sox fans, who saluted him for his previous nine outings. Chicago then got one run back in its half of the fourth to make it 6-2 on back-to-back doubles by Abreu and Brett Lawrie, but Tomlin escaped when two base-running gaffes on Avisail Garcia's ground ball to shortstop led to an inning-ending double play.
That was the White Sox's last real threat.
NOTES: Cleveland 2B Jason Kipnis wasn't in the starting lineup, but manager Terry Francona said it was a scheduled day off with the White Sox starting ace LHP Chris Sale. Francona said SS Francisco Lindor is scheduled to get a day off Wednesday in the series finale for the same reason, with LHP Jose Quintana starting for Chicago. ... Francona also gave a day off to starting C Yan Gomes, who has been struggling at the plate recently. Backup catcher Chris Gimenez started in his place. ... The Indians optioned RHP Cody Anderson back to Triple-A Columbus after he started the second game of a doubleheader on Monday and picked up the win. ... Sale is one of just three pitchers since 1913 to win his first nine starts of a season with a 1.58 ERA or lower, joining Eddie Cicotte and Sal Maglie. ... According to Elias Sports Bureau, the pitching matchup of Sale (9-0) and Indians RHP Josh Tomlin (6-0) was just the fourth in major-league history between pitchers who were each 6-0 or better.