Air France (AF, Paris CDG) took delivery of the first of its sixty A220-300s on September 28, 2021, after F-HZUA (msn 55134) was ferried directly from Montréal Mirabel to Paris CDG. It was presented the day after during a media event at the airport.

"It is an absolutely perfect aircraft for our medium-haul markets, the markets within France, and also the European markets," Air France-KLM Chief Executive Ben Smith said, calling the A220 a "formidable" type.

Smith, who is Canadian, was the Chief Operating Officer at Air Canada when that carrier ordered forty-five A220-300s (then still known as CS300) in 2016. He was already at Air France-KLM when the French unit of the holding firmed its order for the type in 2019. The sixty A220-300s will replace all eighteen A318-100s, the remaining thirty A319-100s at Air France, and "some" of its forty-four A320-200s.

Air France said the A220-300 will begin revenue operations on October 31, 2021, and will initially be deployed out of Paris CDG to Berlin Brandenburg Int'l, Barcelona El Prat, Madrid Barajas, Milan Linate, and Venice Marco Polo. During the winter season, the carrier will extend the type's network to Bologna, Rome Fiumicino, Lisbon, and Copenhagen Kastrup. The ch-aviation fleets advanced module shows that a further five aircraft are scheduled to deliver by the end of 2021, and all sixty by the end of 2025. On top of the sixty firm orders, Air France also has thirty A220-300 options and thirty purchase rights.

During the A220 welcome ceremony, Smith told the media that Air France-KLM was still considering raising fresh capital.

"We're looking at some of the options right now, what might be some of the tools to be able to do just that. We plan to carry out another recapitalization in the coming months," he said.