After the United Kingdom entered World War II in September 1939, she was assigned to convoy defence and patrol duties in the Southwestern Approaches through December 1939.

[1][2] In May 1940, Vesper was deployed with the 19th Destroyer Flotilla to Harwich, England, and assigned to the support of the evacuation of troops from France.

On 10 May 1940 she carried a demolition party to Ymuiden in the Netherlands in Operation XD to destroy oil tanks there to prevent their capture by advancing German Army forces, and on 14 May 1940 she took part in Operation Ordnance, the evacuation of forces from the Hook of Holland.

During June 1940, deployed with her destroyer flotilla to Dover and provided gunfire support to the retreating British Expeditionary Force at Le Tréport, France.

[2] Vesper was reassigned to the 21st Destroyer Flotilla at Sheerness in July 1940 for anti-invasion patrol and convoy escort duties in the English Channel and North Sea, which she continued until December 1940.

On 12 December 1942, Vesper, Whitshed, and the destroyer HMS Worcester, the escort destroyers HMS Albrighton and HMS Brocklesby, and the Royal Norwegian Navy escort destroyer HNoMS Eskdale attacked German shipping in the English Channel, with torpedoes from Eskdale sinking the 387-gross-register-ton Sperrbrecher Beijerland (Sperrbrecher 144) west of Le Tréport, France, at position 50°05′00″N 001°09′00″E / 50.08333°N 1.15000°E / 50.08333; 1.15000 (Beijerland sunk) and torpedoes from Whitshed sinking the 1,236-gross-register-ton Gauss (‘’Sperrbecher’’ 178) northeast of Dieppe, Seine-Maritime, France at 50°04′00″N 001°09′00″E / 50.06667°N 1.15000°E / 50.06667; 1.15000.

[4] After Germany's surrender, Vesper did not deploy operationally, and she soon was decommissioned and placed in reserve, being no longer included on the Royal Navy's July 1945 active list.