The Federal Aviation Administration said the problem, which lasted about four hours, was fixed around 9 a.m., but it was unclear how long flights would be affected.
It started when a single circuit board in a piece of networking equipment at a computer center in Salt Lake City failed around 5 a.m., the FAA said in a statement.
That failure prevented air traffic control computers in different parts of the country from talking to each other. Air traffic controllers were forced to type in complicated flight plans themselves because they could not be transferred automatically from computers in one region of the country to computers in another, slowing down the whole system.
Two large computer centers in Salt Lake City and near Atlanta were affected, as well as 21 regional radar centers around the country.
Delays were particularly bad at Hartsfield-Jackson Atlanta International Airport, the world's busiest. The glitch also exacerbated delays caused by bad weather in the Northeast, with airports in the Chicago, Washington, D.C., and New York metro areas reporting problems.
Some flights were more than two hours behind schedule. Airports around the South also reported delays and cancellations.
U.S. Sen. Charles Schumer, D-New York, said the country's aviation system is "in shambles" and the FAA needs more resources to prevent such problems from continuing.
"If we don't deliver the resources, manpower, and technology the FAA it needs to upgrade the system, these technical glitches that cause cascading delays and chaos across the country are going to become a very regular occurrence," he said in a statement.
Despite the problems, the public areas of Atlanta's airport seemed no busier than usual. Travelers ate breakfast and lounged in the atrium, where sisters Sharon Walker and Sheila James waited to take their elderly mother, Rosa Washington, to see their other sister in St. Louis. The trio's 9:30 a.m. flight was delayed until 4 p.m. because of the glitch.
"We were going to be there for a four-day weekend, but now it's getting cut short," James said. "It's just not a good day."
In the public areas of Newark International Airport, where delays are routine, Thursday seemed like a normal day, though several people paced around the terminal trying to rearrange their plans. Passenger Chris Cozzi said he was moved from one Delta flight to another but was still unsure if it would arrive on time in Atlanta, where he would have just an hour to catch a flight to Europe.
"You have to wonder what's the glitch? Glitch is kind of a general term, it could encompass many, many things," he said. "So it is a concern, but I tend to be an optimist."
At Dulles International Airport outside Washington, AirTran canceled Flight 63 to Atlanta and urged passengers to head to nearby Reagan National Airport to catch another flight. Hilda Ruffin of Manassas, a senior citizen who uses a wheelchair, said she lobbied the airline for a free shuttle pass to get to Reagan.
"I really fought for it ... I don't have the money to pay for a cab," said Ruffin, who was on her way to San Antonio.
Passengers were asked to check the status of their flights online before going to airports.
AirTran canceled at least 22 flights and delayed dozens more. Delta Air Lines was also affected. American Airlines spokesman Tim Smith said several hundred flights would be delayed.
Continental Airlines delays averaged about an hour during the early part of the morning. JetBlue Airways said 25 of its flights at Kennedy International Airport had average delays of 60 minutes and delays at other airports were up to 30 minutes. US Airways flights were no longer being affected by the glitch by midday.
Houston's two airports and Dallas-Fort Worth International Airport reported few delays but said things could get worse, especially for travelers headed east. Los Angeles International Airport also reported that delays were likely later in the day. Airports in Europe reported no immediate problems.
The glitch slowed flight plans collected by the FAA for traffic nationwide at its centers in Salt Lake City and Hampton, Ga., outside Atlanta.
It was reminiscent of a software malfunction that delayed hundreds of flights around the country in August 2008.
In that episode, the Northeast was hardest hit by the delays because of a glitch at the Hampton facility, which processes flight plans for the eastern half of the U.S.
The FAA said at that time the source of the computer software malfunction was a "packet switch" that "failed due to a database mismatch."
Associated Press Writers Joan Lowy in Washington, Marcus Franklin in New York, David Koenig in Dallas, Joshua Freed in Minneapolis, Johnny Clark and Dionne Walker in Atlanta, and Matt Barakat in Chantilly, Va., and videojournalist Bonny Ghosh in Newark, N.J., contributed to this report.