The aircraft, believed to be participating in an aviation fair, smashed into the Madrid ring road on Friday morning.
Dramatic images from the scene in Spain show the orange wreckage of the helicopter strewn across the motorway as emergency service workers dealt with the disaster.
One passenger was able to leave the smash on foot while the other was rescued from the remains of the helicopter by firefighters. The driver of the car was also injured, according to fire services.
One of the crash survivors had a light head injury and another appeared to have a broken femur. The third suffered light injuries, the fire service said.
Traffic has been halted in both directions so emergency services can work at the scene.
The accident is believed to have been caused by heavy wind that is thought to have destabilised the helicopter.
Aviation news website On The Wings of Aviation reported: “The Enstrom 280FX Shark helicopter with registration F-HPUX that was participating in the European Rotors fair that was taking place in Ifema has crashed on the M40 in Madrid shortly after taking off.”