The collision happened just after 6 o'clock Thursday night on Genesee Street near the Buffalo Niagara International Airport in Cheektowaga.
Officials shut down part of Genesee Street for more than three hours.
Police say a pick-up truck carrying one driver and a car carrying a driver and a passenger, somehow crashed into each other.
The driver of the car was transported to ECMC and immediately taken into surgery and is in very serious condition. The passenger of that same car, a white woman in her early 20's, died at the scene. The driver of the pick-up truck was also taken to ECMC. No word yet on that person's condition.
Police are not releasing the names of any of the victims involved in the crash pending notification of next of kin. The investigation into the crash is still ongoing.