Co-designated as County Route 24 (CR 24), NY 52 proceeds southeast through the hamlet of Narrowsburg in the town of Tusten as the two-lane Bridge Street.

Now co-designated as CR 111, NY 52 bends northeast through Tusten, remaining a two-lane rural roadway as it climbs slightly out of the river valley.

Crossing the East Branch of Callicoon Creek, which it will follow to its source, NY 52 passes the southern end of Stone Arch Bridge Historic Park.

Turning southeast further, the route passes the northern entrance road Sullivan County Community College, the highest elevation on its entire length at 1,531 feet (467 m),[15] and then descends to the hamlet of Loch Sheldrake.

[5] Now in the town of Wawarsing, NY 52 bends southeast into an area that remains heavily forested[18] along the next 10 miles (16 km) as it gradually descends off the Catskill Plateau to Ellenville.

[19] The route follows a straight course to the southeast past the small residential hamlet of Dairyland, passing a junction with CR 53A (Milk Road).

[5] NY 52 leaves Dairyland, crossing southeast through Wawarsing into the residential hamlet of Greenfield Park and past Windsor Lake, the source of the West Branch of the Beer Kill, which it follows to Ellenville.

East of the lake, the route bends northeastward for two more miles, crossing through some dense woods between steep hillsides and paralleling Old Greenfield Road.

As it begins to descend through dense woods of scrub oak, NY 52 enters the town of Shawangunk, very near the Sullivan County line.

Afterwards a slight descent[29] heralds the Dwaar Kill crossing, the route remains a two-lane rural roadway through northern Orange County.

At Rider Road, a half-mile further on, NY 52 curves further to the southeast, taking it across a wide swath of farmland into the village of Walden, the largest settlement along the route.

A quarter-mile (400 m) beyond, at the first of the route's several crossings of Wallkill tributary Tin Brook, the houses on the north side of the road start to have a deep setback, reflecting a past division of NY 52 at this point.

[33][34] After passing a swampy area in the woods to the north, NY 52 intersects CR 23 (Rock Cut Road), then runs through swamps along the southern shore of Orange Lake on an eastward heading.

Just past the hamlet, NY 52 turns southeast again at a junction with Monarch Drive and enters an area where woods screen residential neighborhoods off the route.

[5] A commercial strip begins shortly after the Thruway, continuing a half-mile past it to the junction with NY 300 (Union Avenue) at the center of the hamlet of Gardnertown.

To the north marinas at Chelsea and New Hamburg are visible on the river's east side, with the Roseton and Danskammer power plants standing out on the west.

They pass briefly through the northern corner of the city of Beacon, where the bridge's tolls ($1.50 for cars paying cash, $1.25 for EZPass users, and more for trucks[40]) is collected from eastbound traffic.

As the expressway bends eastward again, high chain-link fences with concertina wire surround the concrete buildings of another prison, Downstate Correctional Facility, on the north.

[41] A mile and a half (2.4 km) further east, after passing through a rock cut and going over undulating terrain in a woody area, the routes turn southeast into Exit 44.

[5][43] Three-quarters of a mile (1.1 km) later, after bending around Honess Mountain, NY 52 crosses the East Fishkill town line at the hamlet of Wiccopee.

NY 52 turns more to the northeast for a half-mile, then bends slightly southeast past a swampy area that precedes the center of East Fishkill.

[46] After another half-mile, the route turns due south and begins to climb steeply into the wooded foothills of the Taconic Mountains through a narrow creek valley.

After another three-quarters of a mile, NY 52 reaches its highest elevation east of the Hudson, 962 feet (293 m) above sea level, at the Mountain Top Road intersection.

Just past the junction is Lake Gleneida, part of the New York City water supply system, the center of a park on that side of the route.

[5] Similar to many state highways in the region, NY 52 follows a number of roads originally built as private turnpikes during the early 19th century.

After being incorporated by the New York Legislature in 1830,[52] it built and opened a turnpike from Ellenville on the Delaware and Hudson Canal west to Woodbourne in 1838, and later extended it further in that direction to Liberty.

At the end of 2002, a rockslide along the stretch climbing the Shawangunks east of Ellenville buried an 85-foot (25 m) section of the road with an estimated 1,000 cubic yards (800 m³) of rock and dirt.

[73] The village of Walden has noted, in its 2019 Comprehensive Plan, the difficulties created by the oblique intersection at the eastern end of the Route 208 concurrency.

Traffic on northbound 208 comes to a stop sign at the intersection, where 52 comes in from the right at a slightly lower grade and a sharp angle, with the view mostly blocked by a building.

It has prohibited all trucks over 5 short tons (4.5 t) from any road in the village except the two state highways and certain side streets, and continues to monitor the situation with the hope of eventually signalizing the junction.