The destroyer has served in the Mediterranean, Black, and Caribbean Seas, and in 2019 was deployed to the Persian Gulf in response to increased tensions with Iran in the region.

In 2014, the Royal Navy website stated that Duncan would be the first Type 45 destroyer to be armed with the Harpoon antiship missile system.

[38] In October 2016, Duncan, accompanied by the frigate HMS Richmond, was dispatched by the Ministry of Defence to intercept and "man-mark" a fleet of Russian Navy vessels, including their flagship Admiral Kuznetsov, which was passing through the English Channel on its way to Syria.

[40] Duncan sailed from Portsmouth in June 2017 to assume the role of flagship of NATO's Standing Maritime Naval Group 2 (SNMG2), operating in the Black Sea and the Mediterranean.

[44] She resumed NATO duties in January 2018, visiting Mediterranean and Black Sea ports such as Constanța, Souda Bay, and Split, and again took command of SNMG2, returning to Portsmouth on 13 July 2018.

On the programme, the ship's crew frequently claimed that Duncan can detect a "tennis ball-sized object moving at three times the speed of sound, from over 100 miles away.

[52][53] In February 2023, Duncan joined Orion23, France's largest-ever military exercise, held in the light of the Russian invasion of Ukraine.