The route follows north of the reservoir, passing through Sterling before entering Clinton.

In Littleton, Routes 110 and 2A cross the Fitchburg Line railroad tracks before meeting I-495 at Exit 79, beginning Route 110's long relationship with the interstate.

In Lowell, Route 110 joins Route 3A near the Gallagher Transit Center and just north of the northern end of the Lowell Connector.

The change to being a two-lane road thus was most likely due to safety.

In Haverhill, Routes 110 and 113 bend around the Merrimack, meeting I-495 again at Exit 107.

Route 110 then heads into Merrimac, acting as the main street through that town before entering Amesbury.

Route 110A was a short north–south state highway running from Amesbury to Salisbury.