The collision has taken place on a 40mph section of carriageway at Bouldnor, just outside of Yarmouth.
Emergency services have been alerted to the incident, which occurred just before 16:40.
The road is currently blocked in both directions between Victoria Road and The Avenue.
Southern Vectis say that their Route 7 buses will be diverting through Thorley and Wellow to the Horse in Groom until further notice.
UPDATE @ 17:50 – Police and paramedics have now been joined on scene by the Isle of Wight Fire and Rescue Service.
Crews from Freshwater and Newport have been sent to the incident, alongside a Co-Responder.
The road is expected to remain closed into this evening as emergency teams works to free at least 1 person trapped inside a vehicle.
UPDATE @ 19:05 – A man and a woman have been conveyed to St Mary’s Hospital as a result of the crash involving a Vauxhall Corsa, a Mazda Bongo and a Mini One.
The male was extricated from the Corsa, whilst the injured female freed herself from the Bongo camper van.
Fire crews removed the roof of the Vauxhall to free the male casualty with the assistance of the Isle of Wight Ambulance Service, who sent 2 ambulance crews and a duty officer to the scene.
The 2 casualties have now been taken to hospital.
UPDATE @ 20:25 – The road has now re-opened in both directions.