A car, a van and a lorry collided at about 11.40am between the Ford Road roundabout and the Causeway roundabout, close to Arundel railway station, police have said.
Firefighters are working to remove one trapped person from a vehicle while officers are investigating the cause of the crash and trying to keep traffic moving, with calls from Arundel and Worthing being drafted in to help the rescue effort.
Paramedics are on scene, a spokeswoman from the fire service added.
Police are saying long queues are already building up so motorists are advised to find alternative routes if they can.
If you saw the collision please call 101 quoting serial 520 of 15/4 or email [email protected]
Updates to follow.