Defender carried a maximum of 473 long tons (481 t) of fuel oil that gave her a range of 5,870 nautical miles (10,870 km; 6,760 mi) at 15 knots (28 km/h; 17 mph).

The ship was attached to the Mediterranean Fleet in the Red Sea from November 1935 to June 1936 during the Abyssinian Crisis and then visited ports in East Africa for a month before returning to the China Station.

The next month, she joined the 10th Destroyer Flotilla of the Mediterranean Fleet[5] and escorted Convoy US-2 carrying Australian and New Zealand troops to the Middle East through the Red Sea from 12 to 17 May.

[6] On 27 June, together with sisters Dainty and Decoy, with the destroyers Ilex and HMAS Voyager, she sank the Italian submarine Console Generale Liuzzi south east of Crete.

Defender took part in the Battle of Calabria on 9 July as an escort for the heavy ships of Force C and unsuccessfully engaged Italian destroyers without suffering any damage.

Together with her sisters Dainty and Diamond, the Australian destroyer Stuart, and the light cruisers Capetown and Liverpool, she escorted Convoy AN.2 from Egypt to various ports in the Aegean Sea in late July.

[8] During Operation Collar in late November, Defender, the anti-aircraft cruiser Coventry and four other destroyers sailed from Alexandria to rendezvous with a convoy coming from Gibraltar.

On 27 April 1941 Defender and the destroyers Hereward, and Hero, and cruiser HMS Phoebe, covered Convoy GA.14 as it left Souda Bay, Crete, for Alexandria.

A German air attack sank the Dutch troop ship Costa Rica, but Defender, Hereward, Hero and Phoebe rescued all her crew and all 2,600 soldiers.

An Italian destroyer and two torpedo boats attacked the convoy at night as it was transiting Kaso Strait east of Crete, but were rebuffed by the escorts without inflicting any damage.