The giant America-bound Airbus A330-300 was forced to turn around mid-flight and land back in Britain around 30 minutes after take-off as the cabin filled with smoke.
Once back on the ground, the captain ordered emergency chutes to be deployed so nearly 300 passengers and 13 crew could escape onto the tarmac.
This caused scores of flights in and out of the West Sussex airport to be suspended indefinitely, causing disruption for thousands more Gatwick passengers with rival airlines including British Airways.
Fifteen people, many with broken bones, were taken to hospital by ambulance, their injuries are believed to have been caused by the emergency evacuation.
It is understood fire extinguishers were used mid-air to tackle the blaze, which is believed to have broken out in a rear cargo area.
The plane made a safe landing with emergency services on stand-by, and passengers were disembarked, said a Gatwick Airport spokeswoman.
All flights in and out of Gatwick are currently suspended until further notice.
The passengers involved were being looked after in a specially set-up reception area at the airport.
Virgin Atlantic can confirm that all the passengers and crew have now safely disembarked. We can confirm that there have been four minor injuries.
It added: 'Virgin Atlantic is working closely with the authorities to establish the cause of this incident. The safety and welfare of our crew and passengers is Virgin Atlantic's top priority.'
But the incident caused knock-on delays to other airlines operating in and out of Gatwick- with some incoming flights diverted, and others landing at Stansted Airport in Essex instead.
Gatwick operated a reduced service and warned passengers could expect knock-on disruptions and delays.
British Airways warned customers: 'Flight delays, diversions and cancellations are expected so if you are due to travel to or from London Gatwick, please check the status of your flight before leaving for the airport.'
And easyJet's website said its flights were experiencing 'signification disruption' and recommended passengers check the status of their flight before leaving for the airport.
Eyewitness Lorna Willson, 23, who works in a building that overlooks the runway, said she saw the immediate aftermath of the landing.
She said: 'I was just eating my lunch and I noticed the plane - they usually take off quite quickly but this one didn't go anywhere.
'Then I realised all the chutes were out and there were lots of fire engines and police. I think the passengers had been taken off, but you could see a few stewardesses. There was quite a lot of emergency services there.'
An airport staff member said: 'The plane is waiting on the runway. Police officers and other vehicles are surrounding it. It looks pretty serious, but the airport is dealing with it well. They are not letting anyone else through security at the moment.
'It looks like the height of summer here. They have made announcements that all flights are suspended until 3pm and there is a crowd scene.'
The closure is the second to hit Gatwick in three days. Last Friday, all outbound flights were briefly suspended after a hot air balloon drifted into the flight path.
It is the first incident involving a Virgin flight since 2008, when another passenger jet with 320 passengers was forced to turn back to Gatwick Airport less than an hour into its journey because of a technical problem. The plane to Barbados returned to Gatwick to be met by fire crews after the Boeing 747 circled over Gatwick to burn off fuel before landing.
A Korean Airways jumbo jet made an emergency landing at Heathrow airport in January after a mayday call on a transatlantic flight.
The Boeing cargo plane carrying cattle from Chicago to Brussels issued the call over the Bristol Channel when a fire warning light flashed on in the cockpit, before diverting to Heathrow for an emergency landing.
- Tags: Airbus 330 flight emergency Gatwick airport British Airways Virgin Atlantic Lorna Willson
- Categories: Travel
