NY 253 meets Interstate 390 (I-390) and connects to the New York State Thruway (I-90) in the town of Henrietta.

The roadway gradually curves to the east, coming within 50 yards (46 m) of the New York State Thruway (I-90) and serving the highway's Scottsville service area.

Instead of entering the hamlet, NY 253 leaves Erie Station Road and follows an industrial parkway named Thruway Park Drive around the northwestern edge of the community.

This trend begins to cease as NY 253 meets I-390 (and indirectly with the Thruway) at an interchange, and ceases entirely at a junction with Middle Road, a largely alternate route to I-390 between NY 251 in Rush and Calkins Road.

It initially began at NY 36 in the hamlet of Mumford and followed Scottsville–Mumford Road to the village of Scottsville.

It then followed Calkins and Mendon Center Roads to NY 64 south of the village of Pittsford.

[6][7] The bridge carrying NY 253 over Irondequoit Creek in Penfield's Linear Park was closed to vehicular traffic in the 1960s.

It then turned north to follow Whitney and Five Mile Line Roads to the Four Corners of Penfield, where it ended at NY 441.

The new roadway, as proposed, would begin at the junction of Erie Station and East River Roads and parallel the New York State Thruway westward toward the Genesee River, then loop back to the southeast to end at Farrell Road.

In the swap, ownership and maintenance of the former routing of NY 253 on Scottsville–West Henrietta Road was transferred from the state to the town of Henrietta while the East River Road portion was given to Monroe County[15] and is now part of County Route 84 (CR 84).

Due to the presence of historical buildings at the intersection, the junction could not be widened to handle the increased traffic flow.