The route climbs a hill into the Philipstown village of Nelsonville, where it remains Main Street until transitioning into Cold Spring Carmel Road and passing near the southeast border of the Hudson Highlands State Park.

It crosses US 9, locally Albany Post Road, at Mekeel Corners and continues northeast into the woods of the Clarence Fahnestock State Park.

[3] The highway crosses over Clove Creek a few times and turns slightly towards the southeast; however, it soon resumes a northeasterly course as the Cold Spring Turnpike.

The road passes north of Sagamore Lake to hug the western shore of Boyds Corner Reservoir—part of the Croton Watershed of the New York City water supply system.

Shortly thereafter, NY 301 follows the inside of the western fork of the West Branch Reservoir (also NYC watershed) past the former colonial settlement of Coles Mills just south of the Nimham Mountain State Forest, before bisecting the body of water via a causeway.

[6] To resolve the issue, in 1815, the Philipstown Turnpike Company was organized to improve upon a toll road from Cold Spring to the Connecticut border.

[17] The concurrent CR 47 designation was subsequently eliminated; however, the number was later reused for a 0.2-mile (0.3 km) former alignment of NY 301 in Kent Cliffs.

[20][21] In June 2012, the entire roadway was designated as the Hudson River Turnpike by Putnam County with the intent of reminding "drivers of the picturesque landscape and historic areas along its path".