The carrier will offer four daily flights between the airports with additional routes due to commence in the coming weeks.
In November 2021, the airline announced Birmingham airport would be its headquarters and first crew base, with plans to create up to 200 jobs in the region over the next three years.
The launch was celebrated with a ribbon-cutting ceremony attended by Flybe’s chief executive Dave Pflieger and Birmingham airport boss Nick Barton.
Pflieger said: "Today is a big day for everyone at Flybe. After a year of incredibly hard work, we are thrilled to have our fast, quiet and fuel/CO2 efficient Dash 8-400 (Q400) aircraft back in the sky connecting customers to two of the UK’s premier regional cities.
"Over the coming weeks and months our flight schedule will further ramp up as we take delivery of additional aircraft and serve other new destinations from Birmingham including Amsterdam, Avignon, Brest, Edinburgh, Glasgow and Aberdeen."
