The ship saw early service on the Persian Gulf station, but the outbreak of the Second World War saw Deptford serving as a convoy escort in the North Atlantic and the Mediterranean, sinking a German U-boat in 1941.

On 10 January 1934,[a] the British Admiralty ordered a single Grimsby-class sloop, HMS Deptford, to be built at Chatham Dockyard.

[10] The ship could be fitted for minesweeping or minelaying (for which the aft 4.7 inch gun was removed, allowing 40 mines to be loaded) as well as escort duties.

[6][11] The ship's close-in anti-aircraft armament was supplemented by two Oerlikon 20 mm cannon in January 1942, with a further two being fitted in October that year, and two more replacing the .50 in machine guns in 1943.

[14] On 4 June 1936, Deptford carried Sheikh Hamad ibn Isa Al Khalifa, the King of Bahrain to Basra on the first step of a state visit to the United Kingdom.

[14] Deptford recommissioned with a new crew at Bombay in April 1937, and continued to serve in the Gulf until November that year, when she was refitted again, this time at Columbo in Ceylon (now Sri Lanka).

[14] In September 1938 she was refitted at Bombay again,[14] while in November supported three Vickers Wellesley bombers of the RAF flying from Ismalia, Egypt to Darwin, Australia in a successful attempt at the World Flight distance record.

[14] The outbreak of the Second World War saw Deptford being ordered back to home waters, reaching Portsmouth on 16 November and joining the 2nd Escort Division based at Liverpool in December.

[14] On 3 February 1940, Deptford was part of the escort for Convoy OB 84 when she collided with the merchant ship Antigua, receiving slight damage.

The convoy rescue ship Walmer Castle was badly damaged by a German Focke-Wulf Fw 200 Condor long-range bomber and was scuttled by Deptford and the corvette Marigold on 21 September.

The convoy came under heavy and sustained attack by German submarines and aircraft, and by 19 December four U-boats (U-127, U-131, U-434 and U-574) had been sunk for the loss of one destroyer (Stanley) and a merchant ship.

Shortages of fuel and damage caused a number of ships to leave the escorting force, while the Germans continued to order more submarines into the battle.

[31][32] Deptford was under repair until March 1942 when she rejoined Escort Group 36, working on the Freetown, Sierra Leone convoy route.

In December 1944, Deptford returned to the United Kingdom, where she was employed for convoy escort in the English Channel until May 1945 brought the end of the war in Europe.