Quebec provincial police said the accident occurred at around 3:30 a.m., near the Cartier exit of Highway 20.
Police spokeswoman Christine Coulombe said a car slammed into a signal vehicle parked on the side of the highway.
A good Samaritan then stopped his vehicle in the middle of the highway to help the driver of the first car, then that second vehicle was struck from behind by the ambulance, which burst into flames.
The cause of the fire is not clear, however Urgences-Santé spokesman David Sasson said all ambulances carry oxygen as part of their regular equipment, so it's possible a tank exploded.
There was no patient aboard the ambulance at the time.
"The two paramedics were transported, out of precaution, to hospital," Sasson said. "From what we know, they were not injured."
The driver of the car that struck the signal vehicle could face a charge of impaired driving.