Guthrie is coming off a five-inning, one-run performance in Game 3 of the American League Championship Series, a 2-1 Kansas City win.
Vargas will be making his third start of the postseason, and his first ever at AT&T Park. He combined to allow three runs in 11 1/3 innings in his first two starts -- a no-decision in the AL Division Series at Anaheim, then a win in the ALCS-clinching Game 4 at Kauffman Stadium.
Both Guthrie and Vargas will be pitching on 10 days' rest.
Jackson Alexander is an associate reporter for MLB.com. This story was not subject to the approval of Major League Baseball or its clubs.