The 104 designation, whether it be US 104 or NY 104, has shifted from surface streets to freeway and super twos, particularly from Rochester east to Oswego.

To the north, NY 104's name changes to Lewiston Road as it passes the south campus of Niagara University.

At the city limits, NY 104 meets the northbound Robert Moses State Parkway by way of a half-interchange.

[5][6][7] Now in the town of Lewiston, NY 104 comes within view of the Niagara River gorge and begins to run along its eastern rim.

On the opposite side of the plant, NY 104 connects with Interstate 190 (I-190) at exit 25 via Upper Mountain Road and passes under the eastern approach to the Lewiston–Queenston Bridge, which links I-190 with Ontario's Highway 405.

[4] East of Lewiston village, NY 104 follows Ridge Road through a sparsely populated area of Niagara County.

At the Lewiston hamlet of Dickersonville, the extents of the reservation head south, and development along NY 104 increases slightly.

The two routes form a concurrency east to Warrens Corners, a hamlet on the Cambria–Lockport town line, where NY 93 turns south to serve the city of Lockport.

The two routes join for roughly 0.35 miles (0.56 km) into the town of Newfane before splitting north of the hamlet.

Ridge Road continues northeast through a residential district, which gives way to open fields once more at Ridgewood.

NY 104 exits Orleans County 2 miles (3.2 km) later in the same fashion as it entered: by intersecting a state highway.

On the opposite bank, it loses the name West Ridge Road and becomes a limited-access highway known as the Keeler Street Expressway.

NY 104 narrows to two lanes east of Williamson as development along the route declines once more, giving way to open fields and thick forests.

East of Alton, the gap between the two widens as Ridge Road veers north to access Sodus Bay.

Northeast of this location in the town of Wolcott, Ridge Road intersects NY 104 once again, returning to the south side of the route.

NY 104 heads along the Lake Ontario shoreline to the lake-side city of Oswego, the first location with significant development along the route since Williamson.

The route intersects Sweet Road, a connector leading to the campus of SUNY Oswego, just west of the city limits.

[13] The high level of development along NY 104 continues to the Scriba hamlet of the same name, where it begins to become more sporadic and give way to fields and dense forests.

The route continues due east through the rural town of Mexico to the small hamlet of Maple View, centered around the junction between NY 104 and US 11.

Between Red Creek and the hamlet of Union Square (now Maple View) in the town of Mexico, it included most of modern NY 104.

Farther west, the portion of Route 18 from Niagara Falls to Lewiston was included as part of NY 34.

[26][27] US 104 was assigned across Upstate New York in April 1935, extending from Niagara Falls to Maple View via Lewiston, Rochester, and Oswego.

The realignment created a significant overlap with NY 18, which joined US 104 in the vicinity of Kodak Park and separated at Culver Road, where it headed north instead.

The first portion of the super two, extending from the Monroe–Wayne county line at Union Hill to west of Sodus, was built in the mid-1940s and completed by 1947.

In Irondequoit, the portion of the Sea Breeze Expressway (now NY 590) from Empire Boulevard to Culver Road opened in the late 1950s.

Both designations entered the freeway; however, NY 18 followed the roadway north to Culver Road while US 104 progressed south to Empire Boulevard, where it rejoined its former surface alignment towards Webster.

[39][40] The 0.71 miles (1.14 km) of Empire Boulevard between the Rochester city line and the Sea Breeze Expressway remains state-maintained to this day as NY 941B, an unsigned reference route.

The first section from North Goodman Street to the Sea Breeze Expressway was completed by 1968[35][36] while the remainder opened in late 1969.

[49] The segment of I-81 through central New York was built on an alignment that closely paralleled US 11 from the Pennsylvania state line northward to the city of Watertown.

The portion of I-81 near Maple View was completed in late 1961,[50] at which time US 104 was extended 1 mile (1.6 km) eastward over NY 126 to meet the new highway.