West Midlands Ambulance Service were called to the crash at 4.05am on the southbound A46 near Crewe Lane in Kenilworth.
A spokesman for West Midlands Ambulance Service said: “Crews arrived at the scene to find a car that had suffered damage all over and two patients, one of whom was lying in the road.
“That was a man believed to be in his 20s who had suffered a number of serious injuries.
“Ambulance staff assessed him and treated him for head, leg and arm injuries. He was immobilised and given pain relief before being taken to University Hospital Coventry and Warwickshire.
“The doctor travelled with the patient on the back of the ambulance to continue treatment on route.
“The second patient, also a man in his 20s, was in the passenger seat.
“He was treated for a serious head injury together with back and rib injuries.
“He was also immobilised and given pain relief before being taken to the same hospital.”
The crash has closed the southbound A46 between Stoneleigh and Kenilworth, and there are long delays in the area.
There is also slow traffic on the southbound M42 and M40 because of an earlier accident between junction 3a of the M42 and junction 16 of the M40.