The fatal collision happened around 9:16 a.m. on the 6100 block of Harbinson Avenue.
Investigators say a man, in his early 20s, driving a Mercedes westbound on Benner Street ran a red light.
The Mercedes was struck by a Ford E150 van traveling southbound on Harbison.
Chopper 6 over the scene showed both vehicles severely damaged, with the van ending up on its side on the sidewalk.
The driver of the Mercedes was pronounced dead at the scene.
No other injuries have been reported.
The identity of the Mercedes driver has not been released.