A woman was rescued by firefighters following a collision at Arundel.
Two cars were involved in the collision, which happened near to the Hilton Avisford Park hotel in Walberton last night (July 11).
Police closed off the road to make way for the emergency services, including an air ambulance.
A spokesman for West Sussex Fire and Rescue Service said: "We were called to a two-car collision near to the Avisford Park hotel at 6.35pm last night (July 11).
"Three casualties were released before the fire service arrived. One woman had to be rescued by the fire service.
"All four were taken to hospital by ambulance."
A spokesman for Sussex Police said: “The A27 was closed at Walberton, near Arundel, on Thursday evening (July 11) after a collision involving two cars.
“Emergency services, including an air ambulance, were called to the scene near the Fontwell roundabout at 6.29pm where a Peugeot 508 and a Ford Fiesta Zetec had collided.
“The driver of the Ford Fiesta, a 20-year-old man from Arundel, and an 18-year-old woman from Yapton, who was a passenger, were taken to the Royal Sussex County Hospital in Brighton with serious injuries, not thought to be life-threatening at this time.
“The driver of the Peugeot, a 55-year-old man from Chichester, and his 18-year-old female passenger, suffered minor injuries that did not require hospital treatment.”
The road was closed for rescue and recovery work to take place and re-opened fully around 1.40am, police said.
Anyone who witnessed the collision who has not yet spoken to police is asked to email firstname.lastname@example.org or call 101 quoting Operation Glenfield.
South East Coast Ambulance Service have been approached for comment.