NY 64 is a mostly two-lane highway that primarily serves as a connector between the southeastern suburbs of the city of Rochester and the Canandaigua Lake area, home to Bristol Mountain Ski Resort.

In the vicinity of Bloomfield, however, Route 14 initially followed what later became NY 20C in order to access Holcomb.

The route heads to the northwest as a two-lane highway, running in the base of the Bristol Valley, a lowland created by a pair of imposing mountain ranges to the east and west that is home to the Bristol Mountain Ski Resort.

The elevation of NY 64 remains virtually unchanged, however, as it progresses northward.

The three routes head westward across mostly open fields, meeting the southern terminus of NY 444 south of the former village of Holcomb.

In the northeast corner of the town, NY 64 passes through the hamlet of Ionia.

The road stays on a relatively straight path northward as it heads through the rural southern portion of the town of Mendon to the hamlet of Mendon, where NY 64 meets NY 251 in the center of the community.

Outside of the hamlet, the highway maintains a consistent northerly alignment as it runs through slightly more populated areas of the town of Mendon and passes over the New York State Thruway (Interstate 90 or I-90).

The route enters the town of Pittsford a short distance north of the Thruway, at which time NY 64 becomes Mendon Road.