NY 12E begins at the intersection of West Main and Bradley (NY 12) streets in the city of Watertown. It initially proceeds northwest on West Main Street as a four-lane residential and commercial street; however, it becomes a two-lane divided highway at a CSX Transportation railroad overpass just six blocks from NY 12. Past the crossing, the road follows the Black River across the city line and into the town of Pamelia, where it becomes co-designated as CR 190. The highway soon passes under Interstate 81 and narrows to a two-lane undivided road before turning westward into the riverside village of Glen Park. It retains its Main Street name through the community, following a two-lane residential street through the village center and eventually into the adjacent village of Brownville.