The collision, which happened at around 1.30am on the A23 in Warninglid, involved a car and lorry.
Police shut the road completely at 2.30am.
A West Sussex Fire and Rescue Service spokesman said three fire engines were called to the serious collision, along with a heavy rescue unit.
She said: “We received a call about a car which had crashed into a lorry.
“One person has been confirmed dead. Crews left the scene at 4am this morning.”
A Sussex Police spokesman also confirmed one person had died in the collision.
The road has since reopened and traffic has returned to normal.