MSC Virtuosa will sail its inaugural season, featuring an initial six mini-cruises with a stop in Portland, Dorset, from Southampton, starting 20 May.
The four-night sailings have been designed as short getaways for couples and/or friends, taking in the Jurassic Coast and featuring a day out on the beach as part of a "protected excursion".
These will be followed from 12 June by a series of seven-night sailings from Southampton, with embarkation from Liverpool and Greenock, as well as a stop in Portland.
Sailings will operate according to MSC’s new Covid health and safety protocols. They will also be exclusive to UK residents of all agents, with no vaccination requirement.
Sales will open on Thursday (1 April).
Antonio Paradiso, MSC Cruises managing director UK and Ireland, said the line had been "overwhelmed" by the response to its British Isles cruise programme.
"I’m very proud to be able to bring our newest ship, MSC Virtuosa, to the UK so our valued British guests are the first to officially come on board and the first to experience this incredible next generation ship."
MSC said its "social bubble" ashore visits would ensure the same standards of health and safety it insists on onboard, promising "best practices" of health and hygiene.
"These special sailings not only represent a step towards the restart of the cruise industry in a safe and secure manner but also that of the local economies," said Paradiso.
"Bringing a new ship to the different regional ports will enable our guests to discover the best of the UK this summer, showcasing different British ports around the country."
Guests currently booked on MSC Magnifica will be able to transfer their cruise to MSC Virtuosa; MSC Seaview will replace MSC Virtuosa on its previously scheduled northern Europe itineraries sailing from Germany.
Non-vaccinated guests will be required to provide evidence of a negative test for Covid-19 dating to within 72 hours of embarkation.
Guests will also be required to carry "Covid-specific" travel insurance and provide evidence of their cover pre-departure and at embarkation.
