The cruiser saw active service in the East Indies with the British Eastern Fleet, and was involved in the Battle of Madagascar in September 1942.

She then carried out trade protection duties in the Indian Ocean, but returned to home waters, calling at the territory of the Gambia on the way, where West African Chiefs in full regalia led thousands of their subjects to visit the ship named after their colony.

The New Zealand Official History writes: "... HMNZS Gambia was commissioned at Liverpool on 22 September 1943 under the command of Captain William-Powlett, DSC, RN.

Of particular note was the pursuit of the German blockade-runner Osorno, and the pursuit and destruction of another blockade-runner under Captain William-Powlett's overall command, but without actual involvement: "Under the circumstances," wrote William-Powlett, "Gambia, the senior of the four cruisers, was unable to take part in the successful and exciting operation carried out by Glasgow and Enterprise: she could merely play the part of an exasperated listener-in ...’ Gambia subsequently served with the British Pacific Fleet and participated in attacks on Japanese positions throughout the Pacific.

[4] In 1955 she became flagship of the 4th Cruiser Squadron on the East Indies Station, but the decision not to continue the refit of the battleship Vanguard, meant funds were available for a life extension of Gambia and Bermuda, with additional finance and equipment from US assistance to NATO.

In May 1957 Gambia sailed again for the Persian Gulf, becoming the last flagship for the Commander-in-Chief, East Indies, Vice Admiral Hilary Biggs,[7] and returned to Rosyth on 19 September 1958.

The last months of 1960 she served in the South Atlantic and the Home Fleet before entering the reserve in December of that year, her crew largely going to the new cruiser Blake.