The A27 has been closed eastbound near the Sussex Pad traffic lights after a collision involving three vehicles.
Traffic is at a standstill along the A27 Shoreham Bypass, which has been closed at the Manor Roundabout, affecting traffic heading eastbound.
A spokesman for Sussex Police said ambulance crews were on the scene.
A spokesman for West Sussex Fire and Rescue Service said one casualty had been taken to hospital and one was being assessed at the scene.
Queues are reported of at least 15 minutes and increasing, with traffic gridlocked and motorists out of their cars on the carriageway.