In between, NY 13 intersects with Interstate 81 (I-81) in Cortland and Pulaski and meets the New York State Thruway (I-90) in Canastota.

As NY 13 passes out of Horseheads and into Veteran, the amount of development along the roadway becomes sparse, consisting of only small roadside hamlets.

The three routes proceed generally northeastward through the town of Ithaca to the vicinity of Buttermilk Falls State Park, where they intersect the south end of NY 13A, an alternate route of NY 13 through western Ithaca, near the former Tutelo village of Coreogonel at the confluence of Buttermilk Creek and the Cayuga Lake inlet.

At Dey Street, however, the road becomes a limited-access highway as it heads through the northern extents of the city and partially alongside Cayuga Lake.

Southwest of Ithaca Tompkins International Airport, NY 13 downgrades into a divided highway and meets Warren Road at-grade before reverting into a two-lane roadway as it passes south of the airport and exits the Ithaca area.

All three routes turn north onto Church, creating a three-route overlap that lasts for three blocks through downtown Cortland.

Here, the Tioughnioga River splits, with NY 13 following the eastern branch northeast out of the Cortland city limits.

Upon crossing the county line, NY 13 enters the village of DeRuyter, located in the town of the same name, as Cortland Street.

Outside of the village, the street becomes known as Gorge Road and enters a roughly 100 feet (30 m) ravine surrounding the Chittenango Creek.

As NY 13 progresses northward, the gorge deepens, reaching approximately 300 feet (91 m) within Chittenango Falls State Park.

The two routes overlap, following Genesee Street north for several blocks before turning east and paralleling the former Erie Canal out of the village.

NY 13 crosses over the canal shortly afterward, passing into the Vienna community of Sylvan Beach in the process.

The route continues west for another 3 miles (5 km) before terminating at NY 3 in the hamlet of Port Ontario, which is also in the town of Richland.

When state highways in New York were first publicly signed in 1924, NY 13 was assigned only to the portion of its modern routing between Elmira and Cazenovia.

[9] The portion of NY 13 west of Elmira was removed from the state highway system in the early 1940s.

[13][14] In the mid-1980s, the Sullivanville Dam project forced a portion of the route to be rerouted northeast of Horseheads.

Due to the elevated water level caused by the dam, the route had to be moved to higher ground west of the hamlet of Sullivanville in the Town of Veteran.

[15][16] In the early 1960s, a new expressway was built along the eastern shore of Cayuga Lake, bypassing downtown Ithaca on the west and north.

[23] The highway is named Floral Avenue within the city and Five Mile Drive in the town of Ithaca, so named because was part of a five-mile (8 km) long bypass around the Cayuga Inlet on the west side of Ithaca during high lake levels or river flooding.