The 54-year-old man, who was alone in the vehicle, was pronounced dead at the scene.
Police said his next of kin have been informed.
The road was closed for several hours while teams worked to extricate the van from the undergrowth alongside the A259.
Drivers were diverted from the A26 onto the A27 and through Alfriston and Litlington back onto the A259 at Friston, causing lengthy delays.
The route of the A259 has now been reopened and traffic is returning to normal.
A Sussex Police spokesman said: “Anyone who has witnessed the incident, the circumstances leading up to it or has relevant dashcam footage is asked to contact Collision.firstname.lastname@example.org, citing Op Cranmore. to contact uk.”
https://www.theargus.co.uk/news/20777505.a259-incident-man-54-dead-van-crashes-off-road/?ref=rss A259 incident: Man, 54, dead after van went off road