Police, paramedics and two air ambulances were sent to the scene in Wolverhampton Road after the man was hit at around 2.20pm.
They were left with "multiple serious injuries," West Midlands Ambulance Service said. The male driver of the car was unharmed.
A stretch of Wolverhampton Road/Wednesfield Road remained closed for drivers heading towards the city centre two hours later as police investigated the incident.
Photos from the scene show police cars and ambulances parked on the main road next to Heath Town flats, while one air ambulance hovered above the road before touching down on land off Chervil Rise.
The crash happened near Grove Street opposite Campion House, around 60 metres away from Heath Town Asda.
Interactive map of the area:
A West Midlands Ambulance spokesman said: "We were called at 2.22pm to the junction of Wolverhampton Road and Grove Street.
"We were called to reports of a collision involving a car and a pedestrian.
"On arrival we found one patient, a man, who was the pedestrian.
"He has been treated for multiple serious injuries and taken to the Queen Elizabeth Hospital in Birmingham by land ambulance."
Two ambulances, a paramedic officer, the Midlands Air Ambulance Critical Care Car, the Midlands Air Ambulance from Cosford and the Midlands Air Ambulance from Staffordshire attended the scene.
West Midlands Police has been contacted for comment.