It runs from NY 97 in Hancock north over 10 miles (16 km) to a bridge over Cannonsville Reservoir near the former site of the hamlet of Rock Rift in Tompkins.

The route heads northeast, paralleling the Quickway (NY 17) (Future I-86) and following the east branch of the Delaware River's northern bank through the town of Hancock toward the hamlet of Cadosia.

Upon entering the town of Tompkins, the route passes through Kerry Siding, a small community composed of less than a dozen structures.

Farther north, Cadosia Creek reaches its source 2 miles (3.2 km) from the town line and midway between Kerry Siding and Apex, another small hamlet situated on the route.

[2][3] In the floods of 2006 between June 25 and July 5, some of the areas along NY 268 suffered serious landslides and, as a result, was temporarily closed off by the New York State Department of Transportation.