NY 145 is a two-lane highway its entire length, with a passing lane on hills leaving Middleburgh in both directions.

The route follows parts of the Susquehannah Turnpike from Cairo through East Durham and west.

NY 145 proceeds northwest through Cairo as a two-lane asphalt residential street, becoming a commercial/residential mix near a large quarry on the southbound side.

After CR 67A, more residences and industrial buildings begin to appear as the route enters the hamlet of East Durham.

In East Durham, NY 145 intersects with CR 20B, leaving the small hamlet near Golden Hill Road.

NY 145 winds northwest through Durham, passing a large industrial complex before crossing into the fields and residences nearby.

After crossing a short residential stretch to the north, NY 145 intersects with the terminus of CR 352 (Fox Creek Road), entering the hamlet of Preston Hollow.

A short distance to the northwest, the route enters a small hamlet centered around an intersection with CR 19A (Hauverville Road).

The route proceeds west out of the hamlet, intersecting with CR 19 (Stone Store Road), where it bends to the north.

It then starts to wind north, passing the eastern shore of Vlai Pond near Gates Hill Road.

After leaving Franklinton, NY 145 intersects with the southern terminus of CR 50 (Windy Ridge Road).

After a bend to the northwest, NY 145 intersects with CR 1 (Mineral Springs Road) before entering exit 22 of I-88, a diamond interchange.

[3] NY 145 continues northwest through the town of Cobleskill as a two-lane residential/rural road, entering the hamlet of Lawyersville.

At this intersection, NY 145 bends west onto the right-of-way of Rock District, winding past farms on both sides of the highway.

[3] Winding northwest through Seward, NY 145 crosses past residences before intersecting with CR 30 (Gardnersville Road).

On its south end, it was modified to overlap with NY 23 eastward to Catskill on what is now County Route 23B (CR 23B).