Rick Porcello (9-6) picked up his ninth win by scattering eight hits and three runs over six innings. Phil Coke and Al Alburquerque pitched the last three innings to complete the game.
Cabrera took Oakland starter Guillermo Moscoso deep to left field with a two-run, 422-foot shot that put the Tigers up 4-3. After a Victor Martinez double, Guillen belted another two-run homer to right-center, a 400-plus footer to one of the deeper sections of Comerica Park.
Detroit got on the board first in the fourth inning in a pretty amazing fashion. Martinez singled to reach first base, then scored with a pretty amazing "slide" after A's first baseman Connor Jackson misplayed Guillen's grounder.
The A's took their only lead in the top of the fifth inning on Hideki Matsui's two-run single. Brennan Boesch doubled in Austin Jackson in the sixth inning for the Tigers' final run.