Both P&O Cruises and Saga Cruises resumed sailings on Sunday (27 June) for the first time since the beginning of the pandemic in March 2020.
Saga’s Spirt of Discovery departed from Tilbury and will call at Portsmouth, Portland, the Isles of Scilly and Falmouth while P&O’s Britannia set off on a four-night sailing from Southampton.
Britannia will sail a series of three-, four- and seven-night UK coastal cruises until 25 September when it begins its western Mediterranean itineraries.
Paul Ludlow, P&O Cruises president, said the line has been on "countdown to this moment".
"A huge thank you to our guests for their patience as we fully recognise that it’s been a period filled with anticipation and thwarted plans," he added.
"We’ve spent this time working hard refining and enhancing our holidays so time onboard can be enjoyed to its fullest."
Britannia’s Iona will depart on its maiden voyage on 7 August for a seven-night coastal cruise before beginning Atlantic coast holidays.
Spirit of Discovery’s sister ship Spirt of Adventure will leave on its inaugural cruise on 26 July.
Nigel Banks, chief executive of Saga Cruises, said there "really is no better place to see our beautiful coastline than from the sea".
"We work to the highest standards, and every detail has been thought through to respect current social distancing rules," he added.
"Our guests are so excited to be back cruising again and our crew members are all looking forward to giving them an incredible experience onboard."