The first passenger flight from Doha to Cardiff lands on Tuesday.
A Qatar Airways Airbus A350-900 - with wings made at the manufacturer's plant in North Wales - is due to land in the Welsh capital at 12.50pm.
The service will return to the Middle East at 3.55pm.
Welsh Secretary Alun Cairns, who is on the first flight, said: "Wales is on the fast track to new opportunities in the Gulf.
"The new flight from Cardiff to Doha plugs our entrepreneurs straight into one of the most dynamic economies in the Middle East, and an airport which offers a further 150 global destinations.
"Qatar wants to diversify its economy away from oil and gas and branch out into healthcare, education, sporting events and other areas.
"This presents unparalleled opportunities as these are all growth areas for Wales.
"Our financial services sector in Cardiff is one of the fastest growing outside of London, we have outstanding universities keen to take Qatari students, we have a world-renowned tourism sector and a proven ability to host international sports events."
The route will go on to be served by Boeing 787 Dreamliner aircraft.
It was scheduled to be a daily service, but this has been scaled back to five flights per week until next month due to a delay in aircraft deliveries.
Qatar Airways already serves London Heathrow, Manchester, Birmingham and Edinburgh, with flights from London Gatwick beginning on May 22.