It extends for 23.85 miles (38.38 km) from an interchange with Interstate 290 (I-290) in the town of Tonawanda to an intersection with NY 18 on the shore of Lake Ontario in the village of Wilson.

[3][4] The route begins in the town of Tonawanda where the two-lane Colvin Boulevard crosses the Youngmann Expressway (I-290).

At this point, Colvin Boulevard becomes a four-lane divided highway as it carries NY 425 through the interchange.

Colvin Boulevard forks from NY 425 just north of the junction, giving way to the Twin Cities Memorial Highway.

[5] While on the peninsula, NY 425 serves predominantly commercial and industrial areas built up alongside the Twin Cities Highway.

It encounters two roads here: Fillmore Avenue at an at-grade intersection and East Niagara Street at a partial, northbound only interchange on the southern edge of Tonawanda Creek.

All junctions along the Twin Cities Highway in North Tonawanda are signalized at-grade intersections, with the parallel Division Street serving as a collector/distributor road for NY 425 northbound.

The development that lined NY 425 in North Tonawanda initially continues into Wheatfield, a product of urban sprawl, but it becomes less dense and eventually dissipates as the road heads away from the city.

A few miles beyond NY 93, it finally reaches the village of Wilson, located on the southern shore of Lake Ontario.

NY 425 becomes Lake Street and serves as the main north–south route through the densely populated community.

[25] Although the connection was never built, evidence of the initial plans are visible at the respective termini of each highway.