The new route, operated by WestJet, flies between Cardiff Airport and Toronto.
Passengers on the inaugural flight from Toronto were welcomed with a traditional water cannon salute and a performance of Welsh songs by Penarth choir Criw Canu.
Adam Price MS, Cabinet Minister for enterprise, connectivity and energy, said: “WestJet’s inaugural flight from Cardiff to Toronto is a powerful signal to the world that our nation is open for business.
“Direct transatlantic connectivity like this is exactly what Welsh businesses need to reach new markets, attract investment and grow and it reinforces our ambition to make Wales one of the best-connected economies in the UK.”
WestJet will operate the Toronto route four times a week using its Boeing 737-8 MAX aircraft, offering passengers connections to more than 100 destinations across Canada and the United States via Toronto Pearson International Airport.
Jon Bridge, chief executive officer of Cardiff Airport, said: “Today is a landmark moment for Cardiff Airport and Wales.
“The arrival of WestJet’s direct service gives customers easier access to Toronto and onward destinations across North America, it firmly strengthens Cardiff Airport’s position as the international gateway for Wales.”
Guests and dignitaries, including Ontario’s Agent-General in London Sophia Arvanitis and Cllr Lis Burnett, leader of Vale of Glamorgan Council, attended the celebrations at the airport.
Chris White-DeVries, WestJet senior manager hub strategy and airport affairs, said: “The launch of service between Cardiff and Toronto is an exciting milestone both for WestJet and the communities the route serves.
“WestJet’s new seasonal offering makes it easier for more people to discover everything South Wales and Canada have to offer.”
