Police spokeswoman Sgt. Linda Jackson said the impact caused the ambulance to roll onto its side and slide into an unoccupied parked vehicle, trapping both medics inside. Firefighters pried both victims out of the wreckage and they were taken to nearby Wishard Memorial Hospital in critical condition.
Public safety officials identified the medic who died as Tim McCormick, 24, an Eagle Scout from New York who attended St. Lawrence University. McCormick was driving the ambulance, officials said.
The other medic who was in the ambulance was hospitalized in critical condition with severe head injuries, officials said a news conference. That medic's name was not released.
No one else was in the ambulance. Both medics were wearing seatbelts, police said.
The car's driver was taken to the hospital for a blood test, which is routine in such accidents.
Public Safety Director Troy Riggs said McCormick's death is the first known line-of-duty death of an emergency services worker in the city's history. He said medics, police and firefighters are a family.
"Today a member of that family is missing," Riggs said. He said McCormick's death will be handled like that of a police officer or firefighter.
Maggie Lewis, president of the City-County Council, mourned McCormick's death in a public statement.
"Emergency responders dedicate their lives to caring for the health and safety of everyone in our community," the statement said. "The loss of life in the line of duty is a reminder of how precious life is and that we must live every day to its fullest."