The Federal Aviation Administration said it was working to restore its Notice to Air Missions system which alerts pilots of potential hazards along a flight route.
Some 4,948 flights within, into or out of the US have been delayed, according to a flight tracking website, and 868 cancelled.
All flights across the US were grounded due to a glitch with the Federal Aviation Administration's computer system this morning.
All outbound flights were grounded until around 9am Eastern Time (2pm GMT) as the Federal Aviation Administration worked to restore its Notice to Air Missions (NOTAM) system, which alerts pilots of potential hazards along a flight route.
As of 3pm GMT 4,948 flights within, into or out of the US have been delayed, according to flight tracker FlightAware.com, while 868 have been cancelled. Most delays were concentrated along the East Coast.
"Normal air traffic operations are resuming gradually across the US following an overnight outage to the Notice to Air Missions system that provides safety info to flight crews," the FAA said.
"The ground stop has been lifted. We continue to look into the cause of the initial problem."
Earlier it said "final validation checks" were being carried out and the system reloaded after "operations across the National Airspace System" were affected.
'Almighty mess' for US aviation industry
Sky News correspondent Mark Stone, who was at Ronald Reagan Airport in Virginia, said: "Well an almighty mess for the aviation industry in the United States.
"As of this morning we were told that the NOTAM system had failed, which is part of the air traffic control system. This is critical for flights to be able to take off safely. So as a consequence the busiest airspace in the world, the airspace over the United States, didn't open as it should have done this morning.
"Looking at the flight tracker websites it was very clear you could see flights clustered around many cities around the United States and none of them taking off. Chaos for passengers, as you might imagine."
No evidence of cyberattack
US President Joe Biden has been briefed on the outage, his press secretary Karine Jean-Pierre said.
She said there was no evidence a cyberattack was behind the glitch, "but the president directed [the US Department of Transport] to conduct a full investigation into the causes".
Mr Biden told reporters earlier: "Aircraft can still land safely, just not take off right now. They don't know what the cause of it is, they expect in a couple of hours they'll have a good sense of what caused it and will respond at that time."
The president added that he had spoken to Transportation Secretary Pete Buttigieg on the phone, and told him "to report directly to me when they find out".
Several people tweeted to say they had been stranded due to the outage, with one passenger at Paris' Charles de Gaulle airport saying no flights were flying to the US.
A total of 21,464 flights were scheduled to depart airports in the US today, according to aviation analytics firm Cirium.
Nearly 2.9 million seats are available on those departures.
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