During her inaugural season, Crystal Serenity held summer cruises in Europe, the Mediterranean Sea, and a transatlantic crossing.

It was followed by two Caribbean/Panama Canal voyages and a combined Christmas/New Year Mexican Riviera cruise, round-trip from Los Angeles.

[1] On 14 January 2004, she embarked on her first world cruise; a 106-day voyage departing Los Angeles, which concluded on 5 May, in New York City.

Starting on 10 August 2016, the ship sailed from Vancouver to New York City with 1,700 passengers and crew, taking 28 days for the journey.

In the Canadian Arctic she made stops at Ulukhaktok and Cambridge Bay on Victoria Island, then passed up Franklin Strait and through the narrow Bellot Strait, adjacent to Zenith Point, the most northerly extension of North America.

[20] In June 2022 she was sold at auction to CSE Ltd., reported to be a shell corporation for the actual buyer, for $103M USD.