South of Lakeville, the route is a regionally important highway that serves the villages of Livonia and Wayland and the hamlets of Conesus and Springwater.

[5] Past Conesus, the route continues northward across rolling, rural terrain to the village of Livonia, located in the town of the same name.

Here, NY 15 turns west onto Main Street, joining US 20A on a 2.5-mile (4.0 km) overlap along Main Street and Big Tree Road that takes both routes into the adjacent hamlet of Lakeville, located at the northern tip of Conesus Lake.

The two routes split in the center of the community, where US 20A continues west towards Buffalo while NY 15 turns north towards Rochester.

Outside of East Avon, the two highways continue to follow parallel alignments for another 2 miles (3.2 km) to the Monroe County line.

[4] Now in the town of Rush, NY 15 takes on the name West Henrietta Road, which it keeps until the Rochester city line 12 miles (19 km) to the north.

Not far from the exit is the Henrietta town line, at which point the route begins to pass through gradually more developed areas as it enters the outer suburbs of Rochester.

[6] Just north of the community is a junction with Thruway Park Drive, the current routing of NY 253 through the area.

[4] North of Crittenden Road, NY 15 passes through a pocket of residential development that borders I-390 and the adjacent Erie Canal.

While I-390 continues northwest from here, bypassing most of Rochester, NY 15 stays true to its linear northeasterly alignment, crossing the Erie Canal and entering the city's southernmost section.

NY 15 finally breaks from the linear alignment it had followed since southern Henrietta and gradually gets closer to the nearby Genesee River as it heads northward through the neighborhood; however, it makes a sharp turn to the east just south of downtown Rochester to meet South Avenue in the shadow of I-490 and the Inner Loop.

At its east end, NY 15 turns north onto a unidirectional section of Clinton Avenue, passing over I-490 and the Inner Loop before reaching its northern terminus at the intersection of South Clinton Avenue and Woodbury Boulevard (NY 31) in downtown Rochester.

[4] The highway connecting Lawrenceville, Pennsylvania, to Rochester by way of Springwater and Avon was originally designated as NY 4 when the first set of posted routes in New York were assigned in 1924.

[22][23] In 2009, NYSDOT elected to remove the NY 15 signage along the Southern Tier Expressway and I-390, effectively moving the signed terminus to I-390 in Wayland as well.