The A22 between the Batts Bridge and Lampool roundabouts at Maresfield, was closed for nearly five hours after the accident on Saturday (30 November).
It happened at around 11.30am when a black Lotus Elise sports car travelling north and a grey Ford Focus estate car travelling south collided near the Batts Bridge roundabout.
The Lotus driver, a 47-year-old man from Newick, suffered serious head injuries and was flown by the Kent, Surrey and Sussex air ambulance to the Royal Sussex County Hospital, Brighton.
The Ford driver, a 57-year-old man from Hartfield, and his front-seat passenger, a 13-year-old boy, also from Hartfield, sustained slight injuries and shock. Both were treated at Pembury Hospital, Tunbridge Wells.
The A22 Maresfield by-pass was closed until 4.15pm while emergency services dealt with the incident.
Anyone who saw what happened or who may have dash-cam footage, or who noticed either vehicle being driven shortly before the collision, is asked to contact Sussex Police online or by phoning 101, quoting Operation Ferndale.