Airbus's prototype A350-900 has lifted off from Toulouse Blagnac on its maiden flight, becoming airborne at around 10:00 after a ground run from runway 32L.
The flight is set to take around 4h and test the basic handling and control characteristics of the twinjet.
Typically the maiden flight is conducted under direct and normal flight-control laws, with the airspeed and altitude range expanded as the aircraft's behaviour is confirmed to be stable and corresponding to modelling predictions.
If the flight progresses smoothly the pilots will explore changes in control surface configurations and retract the landing-gear. The jet could even be taken to its maximum operating height of 43,000ft.
A350 programme chief Didier Evrard says the aircraft will "speak to us" during the flight test.
But he says the airframer is confident about the development, saying the "level of uncertainty is not high".
Six crew members, including pilots Peter Chandler and Guy Magrin, have been selected to fly on board MSN1 which is powered by Rolls-Royce Trent XWB engines.
Its first flight will begin a year-long certification programme which will eventually include five flight-test airframes, two more of which are already undergoing final assembly.
Qatar Airways is to take delivery of the first A350-900 in the second half of 2014. Evrard says the cabin for the first customer is "fully defined".
"We have a good grip on the aircraft itself and its customisation," he says.
Airbus is marketing the A350-900 as a 315-seat aircraft and intends the twinjet to have a maximum take-off weight of 268t.