The route is a two-lane highway known as Mill Point Road, named for a small hamlet situated near NY 161's midpoint.

The route heads to the east as a two-lane highway named Mill Point Road, leaving the populated hamlet for more rural, open areas of the town.

[3] The junction once served as the southern terminus of NY 288;[4] however, it now marks the south end of County Route 164 (CR 164).

[3] Past Noeltner Road, NY 161 takes on a more northeasterly alignment, slowly bringing the route down the west side of a shallow valley surrounding Schoharie Creek.

It continues on, crossing the creek and entering the town of Florida before quickly ascending the valley's eastern face.