The southernmost of the highway's two segments begins at an intersection with U.S. Route 6 (US 6) and US 209 in Port Jervis and ends at a junction with NY 55 near the Rondout Reservoir in Neversink.

After passing far east of the Port Jervis station on Metro-North Railroad's Port Jervis Line, NY 42 and NY 97 break off West Main Street for Park Avenue, paralleling the Norfolk Southern Southern Tier Line (ex-Erie Railroad Delaware Division tracks) and Elks–Brox Memorial Park.

A short distance from the change of scenery, NY 42 enters the hamlet of Cahoonzie, which consists of a few residences and dense woods.

After an intersection with Peenpack Trail, the route bends northwest into dense woods, running past ponds and a cluster of homes on the nearby hillside.

[3] NY 42 continues through Deerpark, crossing a creek near Whitehead Road as it winds north and northwest for several miles.

In the hamlet, NY 42 passes several residences on the southern end and in downtown, where CR 108 (St. Josephs Road) intersects.

In Thompson, NY 42 continues northward as a two-lane residential roadway, passing east of Wildwood Lake and to the west of Monticello Airport, which is accessible via Cantrell Road.

After Cantrell Road, NY 42 bends northwest, varying as a two-lane residential and rural roadway through Thompson.

[3] In Thompson, NY 42 continues north, intersecting with the southern terminus of CR 103 (Anawana Lake Road).

In Fallsburg, NY 42 winds northeast past a large residential development, intersecting with the northern terminus of CR 161 (Heiden Road).

At an intersection with Stratton Hill Road, the route and Main Street bend eastward, crossing over the northern edge of Pleasure Lake.

[3] Northeast of South Fallsburg, NY 42 drops the Main Street moniker, making a bend eastward past a large residential complex.

[3] Continuing north through the town of Fallsburg, NY 42 remains a two-lane residential street alongside the Neversink River.

The Neversink forks eastward as NY 42 bends northeast, but both soon rejoin as it passes a small residential segment.

At Couzines Road, NY 42 bends northeast again, passing a large pond, entering the hamlet of Hasbrouck.

In Hasbrouck, NY 42 passes several residences before intersecting with the western terminus of CR 154 (Ulster Heights Road).

Returning to the dense woods, CR 47, bends northeast, then southeast then east as it remains alongside the West Branch.

After a dart to the north, CR 47 bends east and enters a large hairpin turn, where it begins a descent alongside the Esopus Creek.

[5] After the Stephen F. Fischer Memorial Cascade Brooke Bridge, CR 47 continues west through Shandaken, passing several residences before turning northward near Valley View Road.

CR 47 bends northwest, crossing alongside the Esopus Creek past some residences and a tennis court on the western side of the highway.

After another dart to the northeast, CR 47 enters the hamlet of Oliverea, where it intersects with McKinley Hollow Road east of the creek.

After CR 47, NY 42 passes south of Glen Brook Park, continuing northwest through the hamlet as a two-lane residential road.

During this northwestern stretch alongside Halcott Mountain, NY 42 intersects with a former alignment of itself, which parallels to the west for a short distance.

While running east of West Kill, NY 42 remains a two-lane residential roadway, crossing over the waterway once again and intersecting with Beechridge Road North.

[3] When NY 42 was originally assigned as part of the 1930 renumbering of state highways in New York, it was a continuous route extending along a previously unnumbered roadway from Port Jervis in the south to Lexington in the north via Monticello, Neversink, and Shandaken.

[2][6] The section of NY 42 between Neversink and Shandaken was eliminated c. 1934[7][8] due to its low traffic volume and maintenance difficulties arising from the road's high elevation and exposure to severe winter weather.