It is understood the blue sedan was attempting to turn right into the Newmarket Plaza when it was hit by the ambulance.
The blue sedan was then pushed into the tram stop, where a person waiting at the station was pinned by the car.
The man was taken to hospital but died shortly after.
Leading Senior Constable Lee Thomson, a Victoria Police spokeswoman, said the ambulance was “performing urgent duty” when the collision happened. The ambulance collided with a sedan which then hit a pedestrian standing at a tram stop.
“Both of the paramedics have been transported to hospital with minor injuries,” Leading Senior Constable Thomson said.
Two women in the sedan were also taken to hospital with minor injuries.
The Major Collision Investigation Unit is looking into the crash. Ambulance Victoria Acting General Manager Emergency Operations Mick Stephenson said the service would “review this tragedy in detail”.
“Our thoughts and sympathy are with the family of the man at this difficult time,” Mr Stephenson said.