The fire is in a home in the 8300 block of West Balmoral near the airport. At least five ambulances have been sent to the scene.
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CFD spokesman Larry Langford said one firefighter is in critical condition and two others are in fair condition. He said two of the firefighters were in the basement of the home, including the most seriously injured, but it was not clear if they went down there or fell through the floor.
The third firefighter was outside the house and was taken to the hospital to get checked out, Langford said.
Langford said the more seriously injured firefighter was transferred to Loyola Medical Center for further treatment where he is listed in serious condition. CFD has not identified him by name, but said he's a longtime firefighter who has been with the department since the 1990s.
Cell phone video shows smoke coming from the basement of the home.
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"All of a sudden I heard my neighbor screaming, 'My house is on fire!' Like something with the basement," said Jim Bruno, neighbor. "At first it looked like there was smoke in the back, but then they were on the roof and they were cutting holes in the roof. And when they opened the front door, I've never seen so much smoke in my life. Just dark smoke. Unbelievable. I've never seen anything like that in all my life."
The homeowner, who did not want to go on camera, said he has lived in the house for 28 years. He believes the fire, which he said started in the basement, was possibly electrical in nature.
Everyone in the home did make it out safely, officials said. The cause of the fire is still under investigation.
Mayor Brandon Johnson posted on social media, saying he's praying for the seriously injured firefighter's recovery. CFD said the other two firefighters are expected to be OK.