Wanklyn was awarded the Victoria Cross for a patrol in her in 1941, which included an attack on a particularly well-defended convoy on 24 May 1941 in which Upholder sank the 17,879 GRT Italian troop ship Conte Rosso.

[2] The most likely explanation for her loss is that after being spotted by a reconnaissance seaplane, she fell victim to depth charges dropped by the Italian torpedo boat Pegaso northeast of Tripoli on 14 April 1942 in the position 34°47′N 15°55′E / 34.783°N 15.917°E / 34.783; 15.917, although no debris was seen on the surface.

A third and less likely theory came from an alleged air and surface attack on a submarine contact by German aircraft and the escort of a convoy on 14 April off Misrata, but no official Axis record of this action was found after the end of World War II.

[4] More recent research carried out by Italian naval specialist Francesco Mattesini points to a German aerial patrol supporting the same convoy, comprising two Dornier Do 17 and two Messerschmitt Bf 110 aircraft, that attacked an underwater contact with bombs two hours before the Pegaso incident.

[7] When, on 22 August 1942, the Admiralty announced her loss, the communiqué carried with it an unusual tribute to Wanklyn and his men: "It is seldom proper for Their Lordships to draw distinction between different services rendered in the course of naval duty, but they take this opportunity of singling out those of HMS Upholder, under the command of Lt.Cdr.

She was long employed against enemy communications in the Central Mediterranean, and she became noted for the uniformly high quality of her services in that arduous and dangerous duty.

[8] Quoted by Admiral of the Fleet, The Lord Fieldhouse GCB, GBE probably during the Falklands War: "I can do no better than repeat the unique message following the sinking of HMS Upholder on April 14th 1942 : 'The ship and her company are gone but the example and inspiration remain.