The vessel departed for the first of its planned 23 seven-night summer 2022 voyages to Katakolon in Greece, the Greek islands of Crete and Santorini and Bari in Italy, before returning next weekend to its seasonal homeport.
Antonio Paradiso, MSC Cruises managing director UK and Ireland, said: "We are so proud to see our entire fleet back at sea.
"It has been a challenge given the pandemic ashore but our industry-leading health and safety protocol has put us in a position of strength and confidence whereby all of our vessels are now at sea to give our travel agent partners and their customers what they want – relaxing, enjoyable and, above all else, safe cruise holidays."
Following the cruise industry’s shutdown in March 2020 as a result of the pandemic, MSC Grandiosa became the first ship of any major cruise line to return to sea in August 2020.
The brand will welcome two more ships at the end of 2022 – MSC Seascape and its first liquefied natural gas-powered vessel, MSC World Europa. Sales for both vessels are open.