Firefighters were called out to a house fire in the 8000-block of South Prairie Avenue after flames broke out after 1 a.m.
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One person was wheeled out of the home and into an ambulance. A witness said the other person needed CPR at the scene.
Firefighters said a 21-year-old woman was transported to the hospital, where she later died, CFD said. Authorities have not released her identity.
A 65-year-old man was transported to the hospital in critical condition died after life-suffering burns. No other injuries have been reported.
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Firefighters battled the house fire in some dangerously cold conditions could be seen up on the roof trying to get the flames under control.
The cause of the fire is under investigation. Fire officials have not said if they have been able to determine where exactly the fire started.
Deputy Fire Commissioner Timothy Sampey said CFD has implemented its subzero weather operations, trying to limit firefighters exposure to the cold.
"It's just a team effort, that is the reason why there's not more fatalities and we're able to do what we do and the CPD with the traffic control," Sampey said.
Sampey said when it gets this cold, there is a spike in fires as people use extreme measures to heat their homes. The cause of the fire that left two people dead in the Back of the Yards neighborhood Wednesday has not been determined yet, but firefighters are running from call to call, with CFD tweeting out a picture of four firefighters covered in ice.
"They're cold," Sampey said. "I mean they're human beings and they're gonna be cold and we do the best to provide 'em with the best equipment we can and again we bring more resources in so they're not out there as long."
CFD says they put a game plan in place as they saw the forecast in advance, using CTA warming buses for civilians and firefighters. Meanwhile, they hope to send the message to people to heat their home safely.
"Hopefully the more we educate and the more public education we provide and resources we can give them in alternatives, I think we're better off," Sampey said. "We're better than we were this yer than we've ever been before."