The flights to western France will be introduced in co-operation with the airline’s subsidiaries, CityJet and VLM Airlines.
Christine Ourmieres, Air France-KLM’s UK & Ireland general manager, said the airline is "delighted" to launch the new flight, which is hoped to prove popular with both leisure and business passengers.
"Our flights have been deliberately timed to enable travellers to undertake a day’s business in either city," she said.
Weekday and Saturday flights will depart from London City at 08:25 BST and arrive in Nantes at 11:10 local time. The Sunday flight will leave the capital at 17:45 and arrive in France at 20:30.
The flights will be operated using VLM Airlines’ Fokker 50 aircrafts, which offer a choice of both business and economy class.
Air France will launch its new summer schedule from Toulouse on Sunday (March 29th), which includes 34 daily flights to Paris.