In Troy, it passes by Hudson Valley Community College as well as the headquarters of the 42nd Infantry Division.

After Lansingburgh, US 4 turns left to cross the Hudson River on the Troy–Waterford Bridge, entering Waterford, joining with New York State Route 32 (NY 32) to head north together west of the Hudson.

NY 32 joins again to pass through Schuylerville, after which US 4 splits off to cross the Hudson River one last time.

East of Rutland, US 4 is a two-lane highway, meandering through the Green Mountains, passing by Killington, going through Woodstock and Quechee, crossing the Quechee Gorge, and meeting US 5, I-89, and I-91 at White River Junction.

From Dover to its eastern terminus at Portsmouth, New Hampshire, the road used to be known as Route 16 (now NH 16).

[2]1930–: East Greenbush, New York, following former US 9E, through its former west terminus, to Portsmouth, New Hampshire.