The crash happened at about 3:20 a.m. in the 2000-block of W. Jackson Boulevard, police said.
Police said the ambulance was traveling with activated lights when it crashed into a car heading eastbound.
A 47-year-old male driver and a 55-year-old passenger were uninjured in the crash, police said.
Two CFD members were taken to a local hospital and are expected to be OK.
CPD Area Three detectives are investigating.