The demonstration model of the American company's latest plane left the tarmac of Hong Kong International Airport at 10:30pm (1430 GMT) bound for Heathrow airport on a 20,100 kilometres (12,500 miles) voyage.
The record bid comes with the company battling with Eurpoean rival Airbus as the two giants tussle for control of the lucrative long-range aeroplane market.
The plane will fly on an eastern route over the United States, instead of the regular western route over Russia.
On board the twin-engined airliner were just 35 people, including airline executives, journalists and business clients as well as crew members.
Boeing rolled out its first 777-200LR Worldliner in February. It claims the plane is the longest-range commercial aircraft in the world.