Greyhound participated in the Norwegian Campaign in April 1940, the Dunkirk evacuation in May and the Battle of Dakar in September before being transferred to the Mediterranean Fleet in November.

Greyhound carried a maximum of 470 long tons (480 t) of fuel oil that gave her a range of 5,530 nautical miles (10,240 km; 6,360 mi) at 15 knots (28 km/h; 17 mph).

[5] On 17 November 1937, Greyhound and sister ships Grenade and Glowworm were ordered from their anchorage at Mudros to search for the British steamship African Mariner, which was suspected of smuggling war material to Spain.

[6] She was refitted at Portsmouth Dockyard between 7 June and 23 July 1938 and escorted the ocean liner SS Strathnaver between Malta and Alexandria during the Munich Crisis in September 1938.

[5] On 25 January 1939, Greyhound evacuated employees of the British Embassy and their families from Republican-held Barcelona, as the city was threatened with imminent capture by Nationalist forces during the closing stages of the Spanish Civil War.

On 12 November 1939 she collided with her sister ship, Gipsy en route to Harwich, and her new assignment with the 22nd Destroyer Flotilla, but she was only slightly damaged, and her repairs were completed two days later.

On 30 July the ship, and her sister Gallant, escorted the aircraft carrier Argus to Gibraltar and Greyhound was assigned to the 13th Destroyer Flotilla based there.

In late January, the ship, and the destroyers Juno, Jervis, and Janus, escorted the badly damaged aircraft carrier Illustrious from Malta to Alexandria.

[13] She sank the Italian sailing ship Romagna on 17 April off Apollonia, Cyrenaica as she was conducting an anti-shipping sweep off the North African coast with the Australian destroyer HMAS Vendetta.

[5] The ship escorted the heavy units of the Mediterranean Fleet on 6 May as they provided cover for Operation Tiger, a convoy carrying reinforcements to Egypt.

The ships were en route to rendezvous with the cruisers in the Kythira Strait when she was struck by three bombs dropped by Stukas of StG 2 and sank a few minutes afterwards.