Yvonne Kershaw, a 64-year-old grandmother from Petworth in West Sussex, landed the Virgin Atlantic flight from Cancun in Mexico.
Mrs Kershaw joined the airline in 1990 and was granted command of the Boeing 747 aircraft three years later.
She said it had taken passengers a few years to get used to seeing a woman coming out of the flight deck.
"I suppose normally they would expect to see a silver-haired fox flying the aeroplane in command," she added.
"Breaking down those barriers wasn't easy but nobody ever said it would be.
"What you need is passion about your job, determination and skill."
Mrs Kershaw learned to fly at the age of 19 and after flying small aircraft around Europe and north Africa she gained her commercial pilot's licence and flew executive jets.
When she joined Virgin Atlantic its fleet included only four 747s.
"It's such an iconic aeroplane and it's what I wanted to fly. For decades it was the largest aircraft in the world and the most loved by everybody," she said.
Mrs Kershaw has captained more than 2,000 flights with more than 18,000 flying hours in the jumbos.
She said she was "slightly tearful" after landing her final flight and would miss the role "enormously".
"With long-haul it's not a job, it's a way of life, because you spend so much time away from home with crew. They become part of your extended family."

They compared pictures collected by a US reconnaissance programme with recent satellite data to measure the extent of glacial melt.
They believe the now-declassified images could help to show how other remote regions have changed over time.
The research was presented at the American Geophysical Union Fall meeting in San Francisco.
“This imagery will be getting used more and more,” said Josh Maurer from Columbia University in New York.
The images were taken by a United States spy satellite programme that went by the codename of Hexagon.
During the 1970s and 1980s, it launched 20 huge reconnaissance satellites into space, which secretly snapped areas of interest below.
The images were taken on rolls of film, which were then dropped by the satellites, and collected mid-air by passing military planes.
The material collected was declassified in 2011 and is now being digitised by the US Geological Survey (USGS) for scientists to use.
Among the spy images are pictures of the Himalayas, an area for which historical data is scarce. By comparing them with more recent satellite imagery from Nasa and Jaxa (Japanese Space Agency) scientists have been able to see how the region has changed.
“What we are trying to do is to quantify by exactly how much are the glaciers retreating, how much ice are they losing and at what rate,” said Josh Maurer.
“So we’ve used the images to extract 3D models of the terrain back in the 1970s.
“We can see the height of the glacier ice in 1973, and we take those elevation models, and can take the difference between those and the modern day elevation models, and we can work out how the ice volume is changing over time.”
The researchers have found that the extent of the ice loss has been great.
“At every point on the glacier surface across the whole of the Himalayas a quarter of a metre of water is being lost each year,” said Mr Maurer.
“I wouldn’t say it’s surprising given the climate data we have, but it is very very interesting to see how much ice is lost.
“And populations downstream where they depend on these water resources are going to be affected.
“As the glaciers shrink and retreat, the amount of run-off they provide to these streams will increase in the short term as they melt, but over the next 100 years it will decrease more and more, and that’s going to have a negative impact on water resources.”
He said that the images from the Hexagon programme are now being used by various research groups to track how other parts of the Earth have changed over time.
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The UK's first woman jumbo jet pilot has retired after landing at Gatwick Airport for the last time.
[NEXT_CONCEPT]
Scientists have used Cold War spy satellites to reveal the dramatic environmental changes in the Himalayas.