Miguel Cabrera drove in three runs as the AL Central leaders completed a four-game sweep and opened a seven-game lead over the Indians.
Scherzer (17-1) allowed two runs and four hits in seven innings. He helped the Tigers beat Cleveland for the 12th time in their last 13 meetings.
The Tigers have won 12 in a row for the first time since Sept. 2-14, 2011.
Coupled with a 13-game winning streak by idle Atlanta, this marks the first time in major league history that two teams have had winning streaks of at least 12 games at the same time during a season since May 16, 1884, STATS said. That was the only other time it occurred — the St. Louis Maroons had won 15 straight, the New York Gothams had taken 12 in a row.
Cleveland's futility for the series was summed up when manager Terry Francona let utilityman Ryan Raburn pitch the ninth inning. Raburn retired three straight hitters, striking out Matt Tuiasosopo, in his professional pitching debut and drew a standing ovation.
Cabrera drew a bases-loaded walk during a six-run third and hit a two-run single in the fifth, giving him 105 RBIs this season.
That gave Scherzer a huge cushion. He retired the first nine hitters, struck out five and one. He also recorded the 1,000th strikeout of his career when he fanned Jason Kipnis to end the first.
Scherzer threw 100 pitches, and left with a 2.84 ERA this year. The right-hander is 4-0, allowing four earned runs in 28 1-3 innings, since starting for the AL in the All-Star game.
Zach McAllister (4-7) allowed six runs in 2 1-3 innings, his shortest start of the season.
Asdrubal Cabrera drove in Cleveland's only runs off Scherzer with RBI doubles in the fourth and sixth.
McAllister's short outing forced Francona to empty his bullpen, which was already taxed by Wednesday's 14-inning game. Preston Guilmet, Matt Albers and Marc Rzepczynski got the Indians through the eighth but manager Terry Francona needed one more arm for the ninth.
The 25,131 fans cheered wildly when Raburn fanned Tuiasosopo and retired Hernan Perez and Brayan Pena on groundouts. Raburn became the first position player to pitch for the Indians since Andy Marte threw one inning against the Yankees on July 29, 2010.
The series was billed as a battle between the division's two top teams, but the Tigers sent a clear message.
Detroit rallied off Indians closer Chris Perez in the ninth inning for a 4-2 win on Monday. Justin Verlander allowed one run in eight dominant innings in Tuesday's 5-1 victory. Cabrera's home run off rookie Danny Salazar was the key blow Wednesday and the Tigers went on to win 6-5 in 14 innings.
With the momentum clearly on their side, the Tigers struck early in the finale, sending 11 batters to the plate in the third. Cabrera walked for Detroit's first run before Prince Fielder and Victor Martinez added two-run doubles.
NOTES: Tigers CF Austin Jackson took an extra-base hit away from Nick Swisher in the first when he ran down a drive in front of the wall in left-centre. 1B Fielder made a leaping backhand grab of Asdrubal Cabrera's line drive in the second. ... Detroit SS Jose Iglesias was scratched from the lineup because of a bruised left toe. He was spiked while taking a throw at second Wednesday. ... Tiger OF Torii Hunter was given the day off. "Torii is 38 years old and played 14 innings yesterday, so that's a no-brainer to me," manager Jim Leyland said. ... Leyland said Fielder had the option of being the DH, but chose to play the field. ... The Tigers continue their 10-game road trip with a three-game series against the Yankees. Detroit RHP Rick Porcello (8-6) faces New York RHP Ivan Nova (5-4) on Friday night. ... The Indians wrap up their seven-game homestand with a three-game series against the Angels. Cleveland LHP Scott Kazmir (7-4) takes on Los Angeles RHP Jered Weaver (6-5) in the opener Friday.