Passing Brunswick Hospital, the route intersects with the western terminus of CR 2 (Dixon Street) before entering a cloverleaf interchange with NY 27 (Sunrise Highway).

The route crosses through several commercial districts in North Amityville, proceeding northwest towards the Nassau County line.

Bending northeast and away from the county line, NY 110 continues as a six-lane arterial road, crossing through the town of Babylon into East Farmingdale.

NY 110 continues north through Babylon as a six-lane arterial road past the runway of Republic Airport, passing a small campus of Molloy University.

Entering Airport Plaza, the route continues north into an intersection with the eastern terminus of the western segment of NY 24 (Conklin Street).

NY 110 continues north along Broad Hollow Road, going underneath the LIRR Main Line at the site of its former Republic station, then passing the campus of State University of New York at Farmingdale.

[3] Now in Huntington, NY 110 crosses into East Melville, passing through several commercial strips, entering exit 49S–N of the Long Island Expressway (I-495), a cloverleaf interchange.

After the name change, NY 110 crosses into an interchange with the Northern State Parkway (exit 40) and becomes a four-lane boulevard.

The route proceeds north as a four-lane boulevard for several miles, crossing West Hills County Park and past Walt Whitman Shops.

NY 110 then proceeds northwest along New York Avenue, crossing through Huntington Station through a long commercial strip.

This new project, which was to cost $1 million (1953 USD), would expand the corridor to four lanes from two, as the road had already become the most heavily traveled section of routes in Suffolk County.