The sailing is the first of the six-ship line’s phased restart through to November.
All guests onboard sailing yacht Wind Star were required to be fully vaccinated against Covid-19.
Windstar will sail only with fully vaccinated crews too.
The voyage from Athens will visit Nafplio, Monemvasia and Patmos, as well as they islands of Santorini and Mykonos where there will be shore excursions.
Windstar will sail the itinerary on a near-weekly basis through to October.
Its remaining five ships will make their returns over the coming months, with guests and crew subject to new health and safety measures.