The teenage driver of the car, who was also taken to hospital, has since been arrested on suspicion of drink driving.
Ambulances and five firefighters attended the Bilston Street Island in Wolverhampton city centre after the collision happened at about 6.30am.
West Midlands Police is investigating the male driver of the car has been arrested.
A statement said: "The driver of the car has been arrested on suspicion of drink driving and was also taken to hospital with minor injuries.
"A passenger on the tram also received minor injuries.
"The collision happened around 6.30am in Bilston Street and roads have been closed while emergency services are at the scene."
Police were unable to confirm the ages of the suspect or the injured girl.
Roads around the island remained closed six hours on from the crash.
West Midlands Fire Service said: "The driver of the car was able to extricate himself before our firefighters arrived. On advice of paramedics, we assisted a pregnant passenger, who was not trapped by injuries, from the car who was taken to Queen Elizabeth Hospital, and the car was made safe by our firefighters."
There were long delays on the ring road around the city and on nearby results as emergency services dealt with the incident.
A statement from West Midlands Ambulance Service said: “We were called at 6.32am to reports of a collision involving a car and tram at the junction of Bilston Street and Piper’s Row, Wolverhampton.
"We sent two ambulances, two paramedic officers, a MERIT trauma doctor and critical care paramedic and the Midlands Air Ambulance Critical Care Car.
"On arrival, crews found a teenage girl in a life-threatening condition. Staff worked quickly to administer advanced trauma care to the patient at the scene and en route to Queen Elizabeth Hospital in Birmingham.
"The second occupant of the car, a teenage boy, was treated for injuries not believed to be serious and was conveyed to New Cross Hospital.”
Motorists were advised to avoid the area, and traffic was diverted via the A41.
Further tram services between The Royal and Wolverhampton St George's were suspended.
West Midlands Metro said: "Due to road traffic accident, trams are unable to run between The Royal and Wolverhampton St George's.
"Trams are still running with delays between The Royal and Bull St. Travel to Royals for trams to Bull Street."
West Midlands Police also attended, with officers speaking to Metro staff and helping to manage traffic.
It is at least the fourth time in the last four years that serious crashes involving trams and cars have happened at the Bilston Street Island, which connects the ring road, the A41 Bilston Road, Bilston Street into the city centre and the A454.
Anyone with information is asked to call police on 101 quoting log 591 of September 16.