Route 225 begins at an intersection with Route 2A (Massachusetts Avenue) on the east side of the town of Lunenburg in Worcester County. The two-lane highway's name changes from Old Massachusetts Avenue to Groton Road when it enters the town of Shirley in Middlesex County. Route 225's name is West Main Street between its two crossings of the Nashua River—at the Shirley–Groton town line and closer to the center of Groton—and continues from the latter crossing as Long Hill Road. The highway turns north onto Farmers Row to run concurrently with Route 111, then the two routes follow Pleasant Street, which crosses the Nashua River Rail Trail, until Route 111 diverges onto Elm Street. Route 225 continues on Pleasant Street until it joins Route 119 on Main Street. Near the south end of downtown, the routes meet the west end of Route 40 (Lowell Road).