North of I-86, NY 53 follows Fivemile Creek northeastward into a valley that leads to the rural town of Wheeler.

[3] Over the next ten miles (16 km), the route traverses a series of small hamlets located in otherwise undeveloped and isolated areas of Steuben County.

The route heads north–south through the western edge of the large community, following Main Street through its central business district.

The route breaks from this alignment after four miles (6 km), at which point it turns to the north and crosses into Ontario County.

[3] NY 53 was assigned as part of the 1930 renumbering of state highways in New York to its current alignment from Kanona north to Prattsburgh.