The Royals gave up single runs in the eighth, ninth and 10th innings to lose the lead. They also had a three-game winning streak snapped.
Francisley Bueno (1-1) came on in the ninth for the 12th appearance of his rookie season and he surrendered a leadoff double to Casilla on a 1-1 pitch. Span then drilled a ball to right field to bring home Casilla with the winning run.
Kansas City had a 3-1 lead heading into the eighth, but a bases-loaded walk to Josh Willingham in that inning brought the Twins within one. Trevor Plouffe hit a leadoff homer in the ninth off Greg Holland to tie the score.
Glen Perkins (3-1) gave up a one-out double in the top of the 10th but escaped the jam and wound up being the winning pitcher.