Four people have been taken to hospital after the crash on the southbound carriageway of the A24, at the junction of The Quadrangle, in Findon, at 2pm.
Police closed the road and investigations are ongoing.
The fire service attended, following reports people were trapped in the vehicles but were not required upon their arrival.
A police spokesman said the injuries of the four people involved were not thought to be serious.
Motorists are recommended to avoid the area.