Emergency services, including the air ambulance were called to the scene after a silver Focus and blue Audi S3 crashed on the A5 near Lichfield at around 5.15pm on Friday.
The Ford Focus left the road before ending up on its roof, leading to the closure of the A5 between the A461 at Muckley Corner and the A5148 near Lichfield, as the helicopter landed on the dual carriageway.
The driver of the Ford was treated at the scene by paramedics and taken to hospital by air ambulance.
The man, in his 40s, remains in a stable but critical condition. The driver and passenger of the Audi were uninjured, a spokesman for Staffordshire Police said.
Firefighters from Aldridge and Lichfield Fire Stations were among those on the scene.
In a statement, Aldridge Fire Station said: "The driver of one car was trapped with life threatening injuries. Crews quickly assessed his injuries and gave life-saving CPR until paramedics and doctors from West Midlands Ambulance and air ambulance arrived."
Photos showed the air ambulance on the main road, along with other emergency crews, while another showed the crumpled remains of the silver Ford in hedges away from the road. The road was reopened at around midnight.
Witnesses who may have seen the collision or the vehicles beforehand – or anyone who has relevant dash-cam or CCTV footage – should contact Staffordshire Police on Facebook, Twitter, or by calling 101 quoting incident number 543 of July 15.
Alternatively, email email@example.com.