Santana, who leads the American League in strikeouts with 112, had won four straight starts before losing 2-1 to the Chicago White Sox on Thursday.
The 25-year-old left-hander, who had not lost since June 3, allowed both runs and three hits over eight innings, while striking out 12. Santana has four double-digit strikeout performances and a 1.89 ERA over his last five starts.
“This kid is one of the best pitchers in the American League right now,” White Sox manager Ozzie Guillen said.
With the White Sox idle on Monday, the Twins slipped into first place with their 9-0 victory.
The last-place Royals have lost six in a row and are 1-10 since trading star center fielder Carlos Beltran to Houston on June 24. At the time of the trade, Beltran was leading Kansas City in home runs, RBIs, runs and stolen bases.
Mike Sweeney, who became the club leader in two of those categories after Beltran left, missed his fourth straight game with back stiffness. He is expected to be out at least a couple more days.
The Royals have been outscored 87-30 over the last 12 games, and their 29-51 record is the franchise’s worst through 80 games.
“We have been struggling lately and it showed,” Royals manager Tony Pena said. “We won’t change things, we are not going to quit.”