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.

[3] About 2 miles (3.2 km) from the center of Brownville, NY 12E intersects with CR 53 (Cemetery Road), an east–west highway linking the state route to the nearby village of Dexter.

NY 12E continues on, passing just east of Dexter Cemetery and traversing an undeveloped rural area to reach the hamlet of Limerick.

In the center of the hamlet, the highway intersects with NY 180, a road leading to Dexter in the south and the Thousand Islands region in the north.

In the southern part of Chaumont, the route connects to CR 125, at which point NY 12E begins to pass by a mix of commercial and residential properties.

[3] Through the surrounding town of Lyme, NY 12E reverts to a two-lane rural highway as it proceeds west into the hamlet of Herrick Grove, located 3 miles (4.8 km) from Chaumont.

Here, the highway heads along a short commercial strip and intersects with the southern terminus of CR 5 (Depot and Church streets) off the shore of Chaumont Bay.

After leaving Herrick Grove, NY 12E enters the nearby hamlet of Three Mile Bay, which comprises a few homes and a junction with CR 57 (Carrying Road).

Heading northwest through the rural town, the route crosses over Kents Creek and intersects with CR 4 on its way into the village of Cape Vincent, located at the point where Lake Ontario meets the St. Lawrence River.

It heads north as a two-lane residential street,[3] passing the NRHP-listed John Borland House[7] on its way to the south bank of the St. Lawrence River.

[10] Past James Street, NY 12E follows Broadway through a commercial area that continues to the eastern village limits.

Not far from the eastern town line, the route intersects with CR 9 (Sand Bay Road) and passes the Cape Vincent Correctional Facility and Cedar Point State Park, located on opposite sides of the highway.

After the correctional facility, NY 12E crosses into the town of Clayton, where the route remains a two-lane rural riverside highway.

[3] Past the junction with CR 4, NY 12E bends back to the northeast, passing more riverside residences and a handful of farms before entering the village of Clayton.