Qantas Flight QF9 completed its 14,498km (9,009-mile) journey from Perth in just over 17 hours.
The airline is using the Boeing 787-9 Dreamliner, which is twice as fuel-efficient as the Boeing 747.
It is part of ambitious plans by Qantas to add ultra long-haul flights to its schedules.
The Australian flag carrier’s Chief Executive, Alan Joyce, has called the new Perth-London service a “game-changing route”.
Speaking at an event ahead of the inaugural flight, he said the earliest Qantas flights between Australia and the UK – known as the “kangaroo route” – had taken four days and involved seven stops.
Western Australia’s state government is also hoping to see an increase in tourist numbers as a result of the new direct route.
The historic flight, carrying more than 200 passengers and 16 crew, departed from Perth at 18:49 local time on Saturday.
To minimise the discomfort of such a long flight, the plane is equipped with features that provide improved air quality and lower cabin noise.
Some of the passengers agreed to share data on their sleeping and activity patterns with researchers from the University of Sydney.
They wore special monitors and devices that also recorded data about their mental state, eating patterns and hydration levels.
Some aviation fanatics in the UK were up early tracking the plane’s flight path and anticipating its landing.
“We have a touchdown!!” wrote Twitter user Andrew Leong, who said it was “a milestone in the aviation industry”.
Another user, Leigh Mason, said the achievement was “amazing”, adding: “Hope to fly this one day.”
The Premier of Western Australia, Mark McGowan, tweeted on arrival in London: “A new era of travel and opportunities for Western Australia’s economy has officially begun.”
Those arriving in London in the early hours following their historic flight shared images of the welcome they received at Heathrow Airport. (Courtesy BBC)