Flights resumed after a delay of about four hours, but there were bottlenecks across the air system.
The blaze at the facility in Aurora, outside of Chicago, apparently was set by a man who suffered self-inflicted wounds, Aurora police said. There were no indications that it was an act of terrorism and the blaze was extinguished, they said.
The incident caused major delays at Chicago's O'Hare International Airport, one of the world's busiest, and the domestic hub Midway International Airport, affecting flights from almost every state and routes with Europe, Asia and Latin America.
The fire was set by a contract employee angry about being transferred to Hawaii who tried to sabotage the centre that is crucial for air traffic, local broadcaster WGN reported law enforcement officials as saying.
The employee cut himself while cutting wires and also doused lines with gasoline and set them on fire, WGN reported.
Law enforcement officials are planning a briefing later on Friday and were not immediately available to comment.
There were 1,473 flights into and out of the two airports that were cancelled by 12:22pm. (local time), according to tracking website flightaware.com, leaving thousands of travellers stranded.
"There's cascading delays because nothing can take off bound for Chicago from anywhere," said Doug Church, spokesman for the National Air Traffic Controllers Association, a union of air traffic controllers. "The impact is national and major."
At O'Hare, passengers were scrambling to find alternative transportation or bracing for long delays.
"I'm shocked at how calm everyone is. With everything going on in the world, maybe we're all managing our expectations. It's a fire in Aurora, it's not ISIS," said Cynthia Stemler of the Chicago suburb of Lake Bluff, who was heading to Newark, New Jersey, in a reference to the militant Islamic group at war in Syria and Iraq.
DELAYS THROUGH THE DAY
O'Hare is the main hub for United Airlines and a major hub for American Airlines. From January to August, more than 580,000 flights departed or landed at O'Hare, the city of Chicago said, citing Federal Aviation Administration data.
"We anticipate a significant number of cancellations and delays throughout the day," United said in a statement.
Southwest Airlines Co suspended all flights until noon at Midway and Milwaukee's General Mitchell International Airport, the airline said in a statement. It was not clear what other airlines planned to do.
The FAA said employees were evacuated from its control centre in Aurora when the fire broke out, reportedly at about 6am.
"This has resulted in a ground stop for flights in the area and heading to Chicago," the FAA said in a statement.
Airspace management was transferred to adjacent air traffic facilities, it said.
Crews responding to the fire in the facility's basement found the wounded man, who was transported to a hospital, the Aurora Police Department said. One other person was treated for smoke inhalation.
The three-story facility is ringed by a barbed-wire fence and guarded by uniformed officers.
On May 13, about 700 flights were cancelled at O'Hare and Midway airports after a faulty motor in the heating and cooling system at a flight control centre in Elgin, Illinois, a Chicago suburb, caused smoke to circulate and forced staff to clear out of the building.
