Police say a Toyota Prius, driven by Mitchell, 90, drifted over the center line and crashed into a GMC van.
Both Mitchell and the van driver, Richard Pilichowski, 55, were taken to the Christiana Hospital Emergency Room.
Mitchell was pronounced dead from multiple injuries while in surgery.
Pilichowski was released with minor injuries.
An investigation is underway by the Delaware State Police.
Mitchell served as one of the Tuskegee Airmen and was president of the state chapter of the NAACP for more than 30 years. He was also a key figure in eliminating segregation in Delaware.
Mitchell was also the first black teacher in Delaware to teach white students.
The Associated Press contributed to this report
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