The driver fled the scene of the crash after one of the passengers was ejected from the vehicle. Another managed to get himself out of the car but the third was left trapped and had to be cut free by firefighters.
Two of the male passengers were seriously hurt, including one who suffered a major back injury.
The car was left mangled and the bus stop was destroyed when the crash happened on Woodgate Lane, near Junction 3 of the M5 in south west Birmingham, at around 9pm on Sunday.
Police are now attempting to track down the driver who was behind the wheel at the time.
The three injured men were all taken to Queen Elizabeth Hospital for treatment, where two of them were said to be in a serious condition.
Photos from the scene showed how every part of the white Mercedes involved was damaged, with the passenger-side doors removed and parts of the vehicle metres away from its shell which was surrounded by debris.
The road was closed as collision investigators examined the scene.
A West Midlands Police spokesman said: "We’re investigating after a serious collision in Birmingham last night.
"A Mercedes crashed in Woodgate Lane just before 9pm. It’s understood the driver made off from the scene leaving three passengers injured in the vehicle.
"One man suffered a serious back injury, another has a fracture and the other is not seriously hurt.
"Enquiries are under way to identify the driver and the car has been seized.
"We’ve recovered CCTV for examination to understand what happened in the build up to the crash.
"Anyone who witnessed the crash or the driver making off is urged to get in touch.
A spokesman for West Midlands Fire Service added: "The first crew got there in three minutes.
"This collision involved a car in collision with a bus shelter. The car came to rest on the pavement.
"One man was ejected from the vehicle, one man got himself out and a third was trapped in the vehicle by his injuries.
"They used cutting gear and helped to care for the casualty including oxygen and he was removed from the car onto a stretcher.
"The bus shelter was completely destroyed by the impact and our crews made the car safe."
Three ambulances, two paramedic officers, the hazardous response team and a trauma doctor were sent by West Midlands Ambulance Service.
Anyone with information is asked to contact police online or via 101 quoting log 3892 from June 13.