The first FlyLolo flight from Southampton airport to Skiathos took off yesterday.
Weekly flights to the Greek island will run on Tuesdays until October 2.
FlyLolo chief executive Paul Dendle plans to expand to more than a dozen destinations in the eastern Mediterranean in 2019.
He said: “We’re excited that this is the first ever flight from Southampton to Greece, we see this as an important moment in the development of Southampton airport which provides a stress-free alternative to the London airports.
“It’s a first step for our expansion plans for 14 destinations next year to the eastern Mediterranean.”
Skiathos councillor Spiros Vassiliou said: “This is a connection that I and many others have long hoped for and it has only been made possible because of determination and commitment of FlyLolo and Southampton airport.”
Airport managing director Neil Garwood added: “We are committed to providing more exciting destinations to our customers, and this is the first time we’ve opened up a getaway to the eastern Mediterranean. We are looking forward to continuing our relationship with FlyLolo.”