Emergency services were called to Small Heath Highway at 23:25 BST on Friday after a Porsche Cayenne crashed into a lamppost and rolled over.
West Midlands Police said two men in their 20s had died - one after being taken to hospital.
A further two men who were in the car are being treated in hospital for minor injuries.
The ambulance service said the two men had been ejected from their car when it rolled on to the opposite side of the carriageway.
It said one man was confirmed dead at the scene, while a second was taken to hospital with "extremely serious" injuries.
West Midlands Police said he had later died.
The ambulance service said: "The men had been ejected when the car they were travelling in rolled and came to rest the right way up, on the opposite side of the carriageway.
"The car had collided with the central reservation and a lamppost in the incident.
"Bystanders were already carrying out CPR on one of the men prior to our arrival. It quickly became apparent nothing could be done to save the man and he was confirmed dead at the scene."
They said the second man was in cardiac arrest and had a "significant head injury" before he was transferred to Queen Elizabeth Hospital Birmingham.
The service said two other men, in their 20s, had suffered minor injuries and were taken to Heartlands Hospital.
The road was closed in both directions for several hours while an investigation at the scene was held.
Sgt Paul Hughes, from West Midlands Police, said: "Although this tragic collision happened late in the evening, we know there would have been other vehicles on the road at the time."
He called on any witnesses to contact him.
Two men have died after being thrown from their car when it rolled over on a dual carriageway in Birmingham.