MSC will return to the UK in 2018 with Magnifica sailing its first full season ex-UK programme.
The ship, which launched in 2009, will make Southampton its home for eight months from April until November.
The company also revealed it will operate its first world cruise in 2019.
UK managing director Antonio Paradiso announced the ‘big UK comeback’ at their All Star of the Seas event held on Sunday November 13 onboard the MSC Fantasia in Barcelona.
Paradiso said: “We are coming back to the UK with our ship Magnifica for a whole season, it is a big comeback for us and we are very excited.
“It marks a new dedication from MSC to the UK market and how we want to be one of the most popular cruise lines in the country.
“We have created itineraries that make the most of the British Isles and the best of what are customers can experience out of their own country.
“I am really excited, this is game on for us. I want us to become one of the top three cruise lines in the UK.”
There will be five new itineraries out of Southampton including a 14-day sailing calling at Le Havre, La Coruna, Leixoes, Lisbon, Malaga then Amsterdam and Hamburg.
A North Sea sailing will travel to Stavanger, Bergen, Olden and Alesund in Norway plus a round-UK sailing calling at Southampton, Newcastle, South Queensferry in Edinburgh and Invergordon.
Following the UK sailings, the Magnifica will then host the company’s first ever world cruise from January 2019.
The 119-day itinerary will visit 32 countries with 49 ports of call with some destinations including Panama, San Francisco, Melbourne and Petra in Jordan.
Paradiso said: “This will open up a whole new market for us and it is something we have waited a long time to do.
“We wanted to reduce days at sea so during the 119 days there will be no more than five consecutive days at sea.”
Bookings for the ex-UK Magnifica sailings will be available in early 2017, no set date has been released yet.