G-CIVB will fly to Kemble whereas G-CIVY will fly to St Athan where they are expected to be scrapped.
The jumbo jets left the west London airport shortly after 8.35am on Thursday, as more than 18,000 people watched a livestream of the event on Facebook.
BA said that the jumbo jets, one dressed in "Negus" design and the other bearing Chatham Dockyard livery, took to the skies "one after the other" from Heathrow's 27R runway.
In a rare occurrence, the final two aircraft G-CIVB and G-CIVY, will depart simultaneously from Heathrow's parallel runways before one re-joins the approach for a flypast along the airport's southern runway.
Saint-Etienne : Niang (Rennes) ne viendra finalement pas !
Mais " l'intervention de plusieurs agents a rendu impossible la finalisation de l'opération ", précise Saint-Étienne. L'international Sénégalais Mbaye Niang est dans une situation compliquée avec son club, le Stade Rennais .
Enthusiasts and customers are encouraged to share any special memories or photos of British Airways' 747s at 7.47am and 7.47pm using the hashtag #BA747farewell.
The 747 fleet in airline service peaked in July 1998, with 986 aircraft.
Thousands of British Airways flight crew, cabin crew and engineering teams have worked over several decades on and with the aircraft during their time at British Airways during a period when they represented the heart of the long-haul fleet.
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Alex Cruz, British Airways chief executive, said "This will be a hard day for everybody at British Airways as the aircraft leaves our home at Heathrow for the very last time".
Launched in 1969, the 747-400 aircraft were considerably larger than existing airliners, with a capacity of around 550 passengers.
Speaking on Wednesday, Alex Cruz, British Airways chairman and CEO, said "Tomorrow will be a hard day for everybody at British Airways as the aircraft leaves our home at Heathrow for the very last time". They are being replaced by quieter, more fuel-efficient aircraft.
"The 747s have played a huge role in our 100-year history, forming the backbone of our fleet for over 50 years".
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Cette annonce tragique survient alors que Sophie Pétronin est arrivée vendredi en France, après sa libération jeudi au Mali . Sophie Pétronin , 75 ans, a été libérée cette semaine au Mali où elle avait été enlevée en décembre 2016.