The accident occurred around 10:00 p.m. at the intersection of Polly Drummond and Paper Mill roads in Newark.
The crash involved at least four vehicles including two trucks.
Officials say a flat bed truck hit a pickup truck and other vehicles that were stopped at a red light.
A male driver of one of the vehicles was hit from behind and pronounced dead at the scene.
Four other victims were transported to Christiana Hospital with unknown injuries.
Police continue to investigate.