Trailing 6-5 in the bottom of the ninth, the Indians struck for two runs off Detroit closer Jose Valverde (3-3) to stun the Tigers.
Jason Kipnis began the rally with a leadoff double and came home one out later went Carlos Santana sent a liner off the right field wall that just eluded a leaping Dan Kelly for a triple.
Detroit intentionally walked Michael Brantley and Ezequiel Carrera to load the bases and pulled the outfield in, but Chisenhall sent a solid hit to right-center field for the game-winner.
Esmil Rogers (2-1) collected the victory with scoreless top of the ninth for the Indians, who avoided a three-game sweep.
Miguel Cabrera bashed a score-tying, three-run homer in the seventh for the second-place Tigers, who fell two games behind the American League Central-leading Chicago White Sox.