The vaccination requirement will apply to all Silversea voyages globally, with the exception of sailings departing Australia where protocol is still being reviewed.
Starting 18 June, Silver Moon will sail a series of 10-day eastern Mediterranean itineraries from Greece, including calls in Santorini, Paros, Mykonos and Crete.
The new round-trip itineraries will also feature calls in Cyprus, as well as the Israeli city of Haifa. They will go on general sale from Thursday (15 April).
Roberto Martinoli, president and chief executive of Silversea, said: "In recent months, we have seen the cruise industry resume responsibly in destinations around the world, and we are delighted to announce these new inaugural sailings for our flagship."
He continued: "Vaccinations will play a critical role in ensuring the health and safety of our guests, crew, and the communities we visit, which we prioritise above all else.
"Paired with our science-backed onboard procedures, which leverage the expertise of Royal Caribbean Group’s Healthy Sail Panel, vaccinations will enable our guests to travel deep into the world once again with a renewed sense of appreciation for our beautiful planet."
Silversea said its vaccination requirement was also in line with the US Centers for Disease Control and Prevention’s recommendations for safe international travel.
It stressed vaccinations would form part of set of multi-layered protocol to mitigate Covid-19, which includes enhanced sanitation procedures, increased air filtration, high-quality onboard medical care, and enhanced medical teams on each ship.
