The collision happened shortly after 9 a.m. on the 1000 block of Darley Road.
Video from Chopper 6 showed the Claymont Fire Company ambulance with heavy front-end damage. A damaged car was off the road and at rest in the grass.
The driver of the car was killed, police say.
Two people from the ambulance were taken to the hospital. Their conditions were not immediately available.
An investigation into the cause of this crash continues.
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