The 50-year-old was driving a Vauxhall Corsa when it was struck by a Jaguar S-Type at about 10:20 on Saturday in Irvine.
Two men are thought to have then abandoned the Jaguar before getting into a black Mercedes driven by a third man.
The 50-year-old is being treated at Crosshouse Hospital, where he is in a stable condition.
Police have appealed for witnesses to the crash, which was on Long Drive near the Newmoor Roundabout, to contact them.
Det Insp Mick Carr said: "A man requires hospital treatment following a serious road traffic collision. From what we understand, following the collision, two men abandon the Jaguar car and enter a black Mercedes car, driven by a third man. The men then leave the scene of the road traffic collision, heading north along the B7081.
"Our inquiries are ongoing to establish the circumstances surrounding the incident and we are yet to trace the black Mercedes which left the area.
"Anyone with information surrounding this collision is asked to contact police. If you witnessed the crash and have not yet contacted police, please contact officers with any information you may have."
A man has been seriously injured in a hit and run collision in Ayrshire.