"I looked at the matchups," manager Ned Yost said. "Both of them I felt would be good, but [Detroit] is a predominantly right-handed team and Cleveland is a predominantly left-handed team.
"It worked out fine because this is Guthrie's regular day -- just kind of a better matchup pitching-wise for us."
Guthrie had an 8.44 ERA against the Indians last season. Vargas had a 6.18 ERA vs. the Tigers.
"You put Guthrie in there [against] Cleveland and they're going to put eight lefties against him," Yost said.
After Vargas, the Royals will go with left-hander Danny Duffy and right-hander Edinson Volquez to finish out the Indians series.
Right-hander Yordano Ventura will start on Friday night against Detroit when he is eligible after serving his seven-game suspension.
Jeffrey Flanagan is a reporter for MLB.com. Follow him on Twitter at @FlannyMLB. This story was not subject to the approval of Major League Baseball or its clubs.