The incident happened at around 2.30pm on the A21 near Johns Cross, Robertsbridge.
Police said a 16-year-old boy was arrested on suspicion of a number of offences including dangerous driving, failing to stop, and aggravated vehicle taking.
The road was closed on the A21 both ways between A2100 London Road and B2089 Park Lane.
Police said the stretch of road remains shut today (Friday, March 17).
On its Facebook page, Sussex Police said: “The A21 near Johns Cross will remain closed in both directions due to a serious collision involving two vehicles.
"Three occupants in one of the vehicles suffered serious injuries and were taken to hospital.
“The driver of the other vehicle, a 16-year-old boy, has been arrested on suspicion of a number of offences including dangerous driving, failing to stop, and aggravated vehicle taking.
“His vehicle was involved in a pursuit with police before the collision. We have made a mandatory referral to the Independent Office of Police Conduct (IOPC), as is standard practice in these matters.
“Both carriageways are expected to be closed for some time, so we would ask road users to avoid the area if possible.
“Thank you for your patience and understanding.”
1. A21 collision 3.jpg
Emergency services at the scene of the collision on the A21 Photo: Contributed
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Emergency services at the scene of the collision on the A21 Photo: Contributed
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Emergency services at the scene of the collision on the A21 Photo: Contributed
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Emergency services at the scene of the collision on the A21 Photo: Contributed