The collision took place in Town Lane, Kimberworth at around 10.15pm.
A South Yorkshire Police spokesman said: “A red Vauxhall Astra and a Mercedes Sprinter van travelling in opposite directions were involved in a collision.
“A 27-year-old man was taken to hospital with serious injuries.
“Two other men, aged 17 and 27, were taken to hospital with minor injuries.”
A spokesman for South Yorkshire Fire and Rescue said crews from Rotherham station were called to the scene.
The three people injured in the collision had made their way out of their vehicles and were lying by the side of the road by the time firefighters arrived, added the spokesman.
“We provided first aid until the ambulance arrived. All three people were then taken to Rotherham General Hospital in an ambulance,” he said.
An air ambulance was called to the scene, and provided assistance at the scene but was not needed to transfer the three casualties to hospital.
Members of the public reported seeing the air ambulance land in Kimberworth Park.
Anyone with information is asked to call SYP on 101, quoting incident number 967 of Friday, June 14.