Right-hander Max Scherzer makes his 10th career start game series.
Scherzer, a 12-game winner last season, boosted a personal-best win total to 14 in 2011 with an 18-2 rout of the Chicago White Sox in Sept. 4.
He's 0-1 in two starts since, including a 6-1 defeat at Oakland in his last outing on Sept. 15.
The Tigers, who've already clinched the American League's Central Division, are 5-5 in his last 10 starts and Scherzer, a 27-year-old native of St. Louis, is 4-4 in nine meetings with the Royals.
The most recent matchup came Aug. 7 in Kansas City, when the hosts won, 4-3, after touching Scherzer for four runs on six hits in five innings.
On Tuesday, Eric Hosmer finished 5-for-5 with a three-run homer, powering the Royals to a 10-2 win.
Hosmer's 18th home run of the season capped a six-run fourth inning for the Royals, who had won seven straight games before a loss on Sunday.
Salvador Perez and Melky Cabrera both collected three hits, with Perez matching Hosmer's three RBI.
Luis Mendoza (1-0), making his season debut for the Royals after earning Pacific Coast League Pitcher of the Year honors, gave up two runs -- one earned -- on six hits and walked three in seven innings.
Detroit starter Brad Penny (10-11) surrendered seven runs and 10 hits over four frames.
The Royals counter with righty Felipe Paulino, who seeks his 10th major-league win in his 85th appearance.
The 27-year-old, who pitched last season with Houston and began this year in Colorado, earned his third win of 2011 with a 4-2 win at Seattle on Sept. 10, in which he allowed two hits and two runs -- with 11 strikeouts -- in seven innings.
He got a no-decision in a Kansas City win one start later and the Royals are 4-1 in his last five starts.
Paulino, who's 9-31 in 40 big-league decisions, last pitched against Detroit and got a no-decision in the Tigers' 4-3 win on Aug. 5. He is 1-0 with a 2.63 earned run average against them in two career starts.
Detroit is 10-7 against the Royals this season.