It extends from Schenectady to Waterford by way of a series of local, county, and state highways along the Mohawk River and the Erie Canal.

The byway is intended to showcase the history of the waterway, from Native American times through the creation of the Erie Canal and the role the waterside communities played in the Industrial Revolution and the westward expansion of the United States.

Now in the town of Niskayuna, the byway runs alongside the Mohawk River as it follows County Route 10 (CR 10) northeast to a junction with NY 146 in the hamlet of Aqueduct.

[2] Canal Road ultimately brings the scenic byway to the hamlet of Crescent, where it intersects U.S. Route 9 (US 9).

[2] The north branch of the byway heads east from Crescent, loosely following the riverbank as it proceeds along CR 99 to the hamlet of Halfmoon.

The intersection is the east end of the Mohawk Towpath Scenic Byway and the south end of the Lakes to Locks Passage,[2] an All-American Road connecting Waterford to Rouses Point by way of the Hudson River and Lake Champlain corridors.