The National Air Traffic Services (NATS) said it had identified a problem with its flight processing system and that engineers were working urgently to resolve the issue.
In a later update, NATS said it had "implemented a fix" and that its flight processing system was beginning to recover.
Heathrow, London airports among those hit
Around 425 flights to and from UK airports, including London's Heathrow Airport, were cancelled, affecting services operated by several major airlines, including British Airways, EasyJet, KLM and Lufthansa.
Other affected airports included London Stansted and London City, as well as airports in Manchester, Birmingham and Scotland.
Airports warned passengers to check directly with their airlines for the latest information on their flights amid continuing disruptions.
EasyJet reports delays across Europe
Budget carrier EasyJet said some of its flights were "unable to operate" because of the technical failure, while warning that the disruption had caused delays to flights across Europe.
Several passengers took to social media to report being stranded on the tarmac for hours, with many complaining about a lack of communication from airlines.
At Heathrow, the airport's website showed numerous short-haul flights to European destinations as either cancelled or delayed.
Cause of technical issue unclear
While NATS confirmed that the disruption was linked to its flight processing system, the exact cause of the technical problem was not immediately clear.
Arriving flights did not appear to be affected to the same extent, while the impact was primarily reported among departing services.
With the system beginning to recover after the fix was implemented, airlines and airports continued to advise passengers to check their flight status before travelling.