The twin-engine plane came apart and caught fire mid-flight, witnesses told local media, before crashing in Yorba Linda, a suburb of Los Angeles.
The Cessna 414A took off from the Fullerton Municipal Airport about a dozen miles west of the blaze, Federal Aviation Administration spokesman Allen Kenitzer said.
It is still unclear whether or not the pilot is one of the deceased.
Footage from the scene shows that multiple homes were damaged, one of which was fully engulfed in flames.
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As of noon Thursday, at O'Hare International Airport 1,467 flights were canceled, according to the Chicago Department of Aviation. Jim Hayes, a National Weather Service meteorologist, warned that frostbite was possible within 10 minutes in the intense cold.
The Cessna 414A was said to have taken off from a nearby municipal airport shortly before the crash.
Initially, a report by the Orange County Fire Authority said that only two people had died. The FAA and the National Transportation Safety Board are investigating, he said.
Another tweeted: "Pretty sure we just saw a plane crash into a neighborhood".
Firefighters are planning to search the inside of a Southern California house that burst into flames after being struck by pieces of a small plane that crashed into a neighborhood, killing two people and injuring two others.
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Today, Yorkshire will see "Freezing fog patches clearing slowly, otherwise cold with sunny spells", the Met Office said. A map suggested parts of Devon, Somerset, Gloucestershire, Dorset and south Wales will be among the most affected.
Authorities said two other people were transported to a local hospital with unspecified injuries.
Two other people were injured in the incident. "It shook our house".
The Orange County Sheriff said the plane crashed under unknown circumstances. Viewers can see a man drenching it with water from a garden house.
The main body of the twin-engine plane was found in the backyard of another home not far from the burned house.
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Stillhart said that the ICRC now brings in its own medical supplies and emergency trauma care to support six hospitals located across the country.