Firefighters responded to the blaze about 7:30 p.m. Friday at a six-unit motel in the 1000 block of East Benton Street.
Two people were injured and were taken to Rush Copley Medical Center in Aurora.
They were then airlifted early Saturday from Rush Copley to Loyola Medical Center in Maywood, where they remain in critical condition.
Fire investigators believe it started in a wall heater of the burned-out guest room. The fire did not spread to any other motel units.
The Aurora Fire Department says that the smoke detector in the motel unit that caught fire was not operating at the time of the fire.