Route 225 serves the western Middlesex County towns of Shirley, Groton, Westford, and Carlisle.

The two-lane highway's name changes from Old Massachusetts Avenue to Groton Road when it enters the town of Shirley in Middlesex County.

The highway crosses under Interstate 495 (I-495) with no access shortly before its western junction with Route 110 (Littleton Road).

[1] Route 225 crosses the Concord River and enters the town of Bedford on Carlisle Road.

In the center of Lexington, the highways turn onto Massachusetts Avenue, which they follow southeast parallel to the Minuteman Bikeway through a brief concurrency with Route 2A between Marrett Road and Maple Street.