Paralleling I-190 through the city, the route passes east of D'Youville College and through Prospect Park at the junction with Porter Avenue.

Bypassing all the entrance ramps to the Peace Bridge, NY 266 continues along the two-lane Niagara Street to a junction with Busti Avenue.

A couple blocks north, the route reaches Robert Rich Way, which connects to Broderick Park and the wastewater treatment facility for Buffalo.

At this interchange, NY 266 turns northwest with Niagara Street along Scajaquada Creek and parallels I-190 into the Black Rock section of Buffalo.

[4] Passing General Motors Tonawanda Engine Plant, NY 266 is now known as River Road, crossing over I-190 and providing a ramp to the roadway.

[4] Continuing along the Niagara River, NY 266 bends northeast through Tonawanda, passing south of Isle View Park and crosses over Twomile Creek.