Greg Allen hit a walk-off, RBI single in the bottom of the 11th to give the Indians a 4-3 win over the Red Sox at Progressive Field.
Cleveland took two-of-three from Boston in a potential playoff preview.
Both teams have already locked up postseason berths.
Josh Tomlin earned his second victory in a relief appearance.
The Indians close out the regular season with a six-game road trip beginning with the first of three against the White Sox tonight.
Cleveland has already locked up the AL Central at 87-and-68.
Corey Kluber starts for the Indians opposite Chicago's Dylan Covey.