Santana (2-1) tamed the Red Sox on two runs over seven innings, yielding six hits while not issuing a walk and striking out seven.
Kansas City scored three times in the fourth to erase a 2-1 deficit. Perez provided a tie-breaking, two-run single when he sent a liner past diving shortstop Stephen Drew into center field.
Boston starter Ryan Dempster (0-2) surrendered four runs on six hits over seven full frames, issuing three walks while fanning eight.
David Ortiz went 3-for-4 with an RBI in the loss.
Swim Week Miami Beach 2014 [PHOTOS]