The firm said it had made the “painful” decision after struggling to sell the world’s largest passenger jet and after Emirates chose to slash its A380 orderbook by around a quarter.
Due to the reduction and a lack of order backlog with other airlines, Airbus said it would end deliveries of the record-breaking plane in 2021 - just 14 years after it first entered commercial service.
Emirates is yet to take delivery of 14 of the double-decker aircraft - the wings, engines and landing gear for which are made in the UK.
Airbus said it would “start discussions with its social partners in the next few weeks regarding the 3,000 to 3,500 positions potentially impacted over the next three years”.
The BBC reported around 200 of those jobs are in Britain.
The firm said an increase in production of its A320 model would offer “a significant number of internal mobility opportunities”.
Airbus chief executive Tom Enders said: “The A380 is not only an outstanding engineering and industrial achievement. Passengers all over the world love to fly on this great aircraft. Hence today’s announcement is painful for us and the A380 communities worldwide.
“But, keep in mind that A380s will still roam the skies for many years to come and Airbus will of course continue to fully support the A380 operators.”
Nearly 240ft (73m) long and with space for more than 500 passengers, the A380 stole the title of world’s largest passenger jet from the Boeing 747 when it took its maiden commercial flight from Singapore to Sydney on October 27 2007.
The giant aircraft’s first commercial flight to Europe - a Singapore Airlines service - arrived at Heathrow on March 3 2008.
According to Airbus, the plane has flown more than 500,000 revenue flights and carried over 190 million passengers to date, with more than 300 commercial flights a day.
However concerns over the future of the superjumbo began to appear and in 2016 Airbus announced a drastic cut in production, reducing the build rate by half.
On Thursday, the firm said Emirates had chosen to reduce its order of A380s from 162 to 123 aircraft following a “review of its operations, and in light of developments in aircraft and engine technologies”.
Meanwhile, the UAE carrier is buying more of the smaller A330-900 and A350-900 aircraft, purchasing 40 and 30 respectively.
“As a result of this decision we have no substantial A380 backlog and hence no basis to sustain production, despite all our sales efforts with other airlines in recent years,” Mr Enders said.
“This leads to the end of A380 deliveries in 2021. The consequences of this decision are largely embedded in our 2018 full-year results.”
The Emirates order for the A330-900 and A350-900 is worth 21.4 billion US dollars (£16.6 billion).