Santiago was stopped as he exited in the fifth inning. His glove was confiscated, and it was later announced that Santiago had been thrown out.
The 33-year-old left-hander became the first player to be ejected as part of Major League Baseball’s new foreign substance procedure. Major league umpires last week started regular checks of all pitchers for sticky substances used to get a better grip on the balls, but can also increase the spin of the balls and make hitting them more difficult.
Taylor Trammell homered twice for Seattle, which improved to 10-2 in its last 12 games. Paul Sewald got one out for the win, and Kendall Graveman worked the ninth for his seventh save.
The White Sox lost AL MVP José Abreu when he was hit on his left knee by a pitch in the sixth. The team announced the first baseman had a bruised left knee and X-rays were negative.
The teams played 2 1/2 innings Saturday before the game was postponed because of rain.
Trammell connected for his seventh homer in the fifth, and Ty France went deep against Dallas Keuchel in the sixth. Leury García hit an RBI single in the fifth for Chicago, and Yasmani Grandal added a tying sacrifice fly in the sixth.
The Mariners went ahead to stay when Trammell hit a towering drive into the right-field bleachers with two out in the ninth against Liam Hendricks (3-2). Grandal led off the bottom half with a base hit, but Jake Lamb flied out and Yermín Mercedes bounced into a double play.
The teams will play a seven-inning game for the series finale later Sunday.
Keuchel allowed six hits, struck out four and walked one in his first relief appearance since Aug. 6, 2013.
The AL Central-leading White Sox have dropped seven of eight.
Seattle placed left-hander Marco Gonzales on the paternity list and recalled right-hander Yohan Ramirez from Triple-A Tacoma.
White Sox: RHP Michael Kopech (strained left hamstring) will throw a simulated game on Monday, and manager Tony La Russa said the team will decide whether he is ready or needs a rehab stint with Triple-A Charlotte.
Neither team announced a starter for the second game of Sunday’s doubleheader.