According to Sussex Police, officers received reports of a lorry overturning, before being involved in a collision with a car at 5.40am.
A spokesperson said: "The lorry driver — a 62-year-old man — suffered a serious injury and has been taken to hospital for treatment. His injuries are not thought to be life-threatening or life-changing.
"The car driver — a 50-year-old woman — suffered minor injuries."
South East Coast Ambulance Service said the two patients were assessed and treated at the scene before being taken to hospital.
A spokesperson said: "One patient was taken to St Richard’s Hospital and the second was taken to Southampton General."
West Sussex Fire and Rescue Service said its crews 'released one person from the HGV using small tools'.
A spokesperson said: "[The] driver of the other vehicle self released prior to FRS attendance.
"Crews are now working to contain a diesel leak using environmental packs."
Police said the road is currently closed in both directions and disruption can be expected for a 'number of hours'. Diversions are in place.
Anyone who witnessed what happened can report online or call 101, quoting Operation Milldown.
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