During August 1941 HMS Avon Vale served in the North Atlantic on escort duties.

From 5 until 11 September 1941 she was docked in the Selborne dry dock, Simonstown, South Africa and later that month she was back in the North Atlantic on escort duties.

November saw her back in the Mediterranean where she was engaged in the escorting of the ammunition transport vessel Hanne (1360 tons) from Alexandria to Tobruk, the second escort vessel was the Australian sloop HMAS Parramatta. At midnight of the 26th the convoy was just to the north east of Tobruk, the Australian closed on the Hanne to communicate making about three knots. A torpedo struck the destroyer amidships, fired from the German submarine U-559, the ship was instantly crippled, and she rolled over to starboard and sank within a few minutes. Avonvale did everything possible to pick up survivors, however only 19 were rescued. Hanne with her cargo of ammunition was safely delivered to Tobruk.

During March 1942 whilst a unit of the 5th DD Flotilla Avonvale and other Hunt class destroyers set out from Alexandria for Tobruk on a submarine sweeping operation to clear the wat for the aproaching Malta bound convoy. It was during this operation that U-652 evaded the searchers and launched an attack in which HMS Heythrop was damaged, she was taken in tow but later sank. Avon Vale and her sisters eventually rendevoused with the convoy and her escorts, then only 8 miles from Malta disaster struck, the auxiliary supply ship HMS Breconshire was hit by a heavy bomb in the engine room, totally disabling her, the destroyer HMS Southwold whilst coming alongside, struck a mine and sank. Avon Vale was diverted to the scene and suffered some damage when a bomb narrowly missed her. Of the total of 26,000 tons of stores carried by the four supply ships only 5,000 tons finally reached their destination.

On 29 January 1943 still in the Mediterranean off Bougie, some 100 miles east of Algiers HMS Avon Vale was torpedoed after being attacked by Italian torpedo bombers, she steamed into port with the whole of her fo'c'sle up to her bridge structure blown off.

Avon Vale was allocated to the Royal Hellenic Navy as Aegion from March 1944 until May 1944. She was never commissioned into the RHN. due to the mutinous state of the Greek Navy.

On 6 June 1944 HMS Avon Vale was a member of the escort forces for the landings at Normandy.

In August 1944 she joined the 22nd Destroyer Flotilla at Alexandria.

On 1 November 1944 HMS Avon Vale with her sister-ship HMS Wheatland were patrolling the coastal shipping routes south of Lussino in the Adriatic when they received a signal indicating the possible presence of enemy warships in the area giving cover to vessels evacuating German troops from Yugoslavia and some islands. That evening two enemy corvettes were sighted. (UJ-202 and UJ-208. The two destroyers opened fire at a range of 4,000 yards. The enemy soon replied and soon had the range on Avon Vale. She was near missed by a 4-inch shell which sent splinters onboard. In less than ten minutes the enemy ships were reduced to mere scrap, the two British ships were circling the enemy and pouring out a devastating fire of pom-pom and small calibre gunfire. When the first corvette was sunk Avon Vale closed to rescue the Germans while Wheatland continued to shoot up the second corvette which eventually blew up. Ten minutes later the British came under fire from the German destroyer TA-20 (ex-Italian destroyer Audace) which suddenly appeared on the scene. When the two British ships directed their fire at her, she turned away made smoke and tried to escape. But she suffered a hit early in the action and her speed dropped away. The two destroyers pounced upon her for the kill and it was not long before the enemy destroyer was sunk.

Avon Vale returned to the U.K. in December 1944.

Avon Vale was broken up at Sunderland starting on 15 May 1958.