The men, aged in their 20s, were a driver and passenger in a Toyota Yaris which hit a lamppost on Hagley Road West, near Lightwoods Park in Bearwood, just before 10pm on Tuesday.
Fifteen firefighters, paramedics and police were sent to the scene but the fire had already taken hold when they arrived and the men were pronounced dead at the scene.
A second male passenger was taken to hospital in Birmingham with critical injuries.
West Midlands Police is investigating and has appealed for anyone who was on the road at the time or saw the car beforehand to come forward.
Detective Sergeant Paul Hughes, from the serious collision investigation unit, said: “We’re in the early stages of establishing exactly what happened and we remain keen to hear from anyone who was in the area at the time.
“We’d ask anyone who was travelling along the dual carriageway and saw the red Toyota Yaris before the collision – or has information about the crash – to contact us.
“We would appreciate if drivers could check their dash cams as anything which was captured could assist our enquiries.
“This is a devastating time for the families of the victims and we’d urge people to come to us with any footage, rather than speculate and share potentially distressing material online.”
Fifteen firefighters were sent to the crash along with paramedics and a specialist emergency doctor.
The crash happened on the A456 Hagley Road West near the junction with Winchfield Drive, with photos from the scene showing how the car was destroyed by the blaze.
The road, which connects Birmingham with Quinton and Halesowen, was shut for several hours but was back open by Wednesday morning.
Fire crews from Smethwick, Ladywood and Woodgate Valley fire stations were sent to the blaze, West Midlands Fire Service said, while one ambulance, two paramedic officers, a critical care car from the air ambulance service and a BASICS emergency doctor were sent by West Midlands Ambulance Service.
A spokeswoman for the ambulance service said: “Upon arrival, crews discovered three patients from the car, which was ablaze.
“Two of them, the driver and a passenger in the car, had suffered serious injuries in the collision. Unfortunately, it immediately became clear that nothing could be done to save them and they were confirmed deceased at the scene.
“The third patient, a passenger in the vehicle, received advanced trauma care at the scene for serious injuries before he was conveyed to Queen Elizabeth Hospital Birmingham for further treatment.”