Scherzer (16-6) struck out seven, to increase his Major League-leading total to 220, and allowed just one run in six innings to set the tone for Detroit as they pulled within one game of Chicago at the top of the division.
"I knew this was the biggest start for me this season," Scherzer told reporters. "It's September baseball. I wanted the ball in this situation for that very reason."
The Tigers have won two-of-three in the series heading into Thursday's finale.
Detroit (75-67) took control with three runs in the fifth inning and kept piling it on with Prince Fielder's three-run home run in the seventh for a 6-1 lead.
They moved 8-1 ahead in the top of the eighth but the White Sox (76-66) made a late charge against the visiting bullpen.
Youkilis also homered in the fourth against Scherzer.
Chicago starter Gavin Floyd returned from an elbow injury that had kept him out since August 26, but his outing lasted just 4 2/3 innings.
"We need to come out and win the game tomorrow (Thursday) and we're right back where we started this four-game series," White Sox catcher A.J. Pierzynski said.
