NY 266 begins at the end of the off-ramps for exit 8 of I-190 (the Niagara Thruway) in the city of Buffalo. Running northwest along Buffalo's West Side, NY 266 proceeds along Niagara Street, a two-lane commercial street through the city. Paralleling I-190 through the city, the route passes east of D'Youville College and through Prospect Park at the junction with Porter Avenue. Porter Avenue connects NY 266 to I-190's exit 9 just to the southwest. Bypassing all the entrance ramps to the Peace Bridge, NY 266 continues along the two-lane Niagara Street to a junction with Busti Avenue. At Busti, NY 266 and Niagara Street turn north, running in the shadows of I-190 near the Niagara River. A couple blocks north, the route reaches Robert Rich Way, which connects to Broderick Park and the wastewater treatment facility for Buffalo.