While providing escort for a North Sea convoy on 16th October 1939, MOHAWK was attacked by a German Ju88 aircraft. Before the dive bomber was destroyed, it released two bombs which fell to starboard (abreast of the bridge) and to port (abreast of the torpedo tubes). The bombs exploded on the surface of the sea well before most men had time to reach their action stations. Machine gun bullets and jagged metal splinters decimated the mooring party on the fo'c'sle, slashed through the bridge, the wheelhouse, the director and the communications system. The personnel manning the machine guns, the search light position and after control position were mowed down by the projectiles. Fifteen men were killed and thirty injured, mostly experienced executive officers. On the bridge, Commander Jolly suffered a mortal stomach wound. While denying the comfort of medical attention, and in great pain and suffering, he commanded his ship for 35 miles until she was safely in port. After being taken to hospital at South Queensferry, England, he died several hours later. For his gallantry, the Captain was awarded the George Cross posthumously. The ship was patched up at Rosyth then made her way to the Hawthorn Leslie Yard on the Tyne river for permanent repairs and a refit.

Early in 1940, MOHAWK was engaged in a number of convoy escorts and fleet sweeps in the North Sea and Atlantic Ocean. On 3rd March, she helped escort the brand new liner QUEEN ELIZABETH out of the Clyde River and remained with her until the first stage of the voyage to New York City was complete. MOHAWK almost missed this great opportunity as a result of a collision with the steamship SS GARTBRATTAN. MOHAWK carried out her assignment in a slightly damaged state then set sail for repairs at Troon.

The British Admiralty, anticipating Italian aggression in the Mediterranean, decided to move destroyers there to help screen the big ships. MOHAWK and HMS NUBIAN, as part of the 14th Destroyer Flotilla (14th DF), were among the first vessels selected to escort capital ships in this area. At 1645 on 10th June 1940, Italy declared war on the United Kingdom starting at 0001. By 0100, the Mediterranean Fleet was at sea and approached to within 120 miles of the Italian coast, then returned to Alexandria, Egypt on the 14th June. On the 8th of July, the British and Italian Fleets clashed in the Battle of Calabria, In the ensuing conflict, the Italian navy made smoke and their ships raced for cover. MOHAWK and NUBIAN were instructed to open fire if any of the enemy ships darted out of the smoke in order to fire torpedoes on British ships.

For the next month, the 14th DF was involved in a series of sweeps and patrols in the Eastern Mediterranean hunting for U-boats and surface ships. Sometimes they were attacked but action was scarce. On 27th August, MOHAWK and the other ships of the 14th DF left Alexandria for a fast passage to Gibraltar in order to team up with other ships already there. This large force provided escort coverage for the next convoy to Malta. From 19th to 27th October, there was a brief quiet time for the ship and minor repairs were carried out at Alexandria. This lull ended on the 28th when Italy attacked Greece. Immediately, the fleet sailed sweeping right into the Ionian Sea but no Italian forces were encountered. By 6th November, the Mediterranean Fleet had left Alexandria to provide cover for convoys crossing to and from Malta. On 11th November, MOHAWK and other capital British ships detached from the Commander-in-Chief and headed for the Straits of Oranto with the objective of "enhearting the Greeks and dealing the enemy a blow in his own waters." After a short skirmish with the Italian navy, the Fleet returned to Alexandria on 14th November.

At 0500 on 7th January 1941, the battlefleet once again sailed from Alexandria to cover a complicated movement of convoys to and from Greece and Malta including the Excess convoy which passed right through the middle of the Mediterranean. Again, there were German air attacks and engagements with Italian destroyers and torpedo boats. Luckily, the Fleet returned to Alexandria somewhat damaged but without having lost a single merchant ship to the enemy.

MOHAWK'S luck changed very suddenly. On 10/11 April, she and HMS JERVIS, HMS JANUS and HMS NUBIAN arrived at Malta to act as a night striking force. After two night patrols nothing was sighted, however, on 15th April, Allied reconnaissance located a Tripoli bound convoy off Cape Bon. The 14th DF left Malta in search of the enemy and made contact just off the coast of Africa. A fierce battle developed with the Italian navy. Smoke, explosions, shell splashes, burning ships and torpedoes confused the night sea. During the action, MOHAWK evaded a bow ramming from the lead German merchantman in the convoy. Just as the destroyer opened fire, a torpedo hit her just abreast of 'Y' mounting on the starboard side. The whole of the stern from the superstructure aft was blown away and MOHAWK was awash as far as 'X' mounting. The crew of 'Y' gun and the supply party were all killed. 'A' and 'B' guns continued firing on the merchantman and set her on fire. During this time, MOHAWK had been motionless in the water. Just as the destroyer made an attempt to get under way, a second torpedo arrived hitting portside between No.2 and No.3 Boiler Rooms. The No.3 boiler burst, scalding people on deck. The centerline of the upperdeck split open allowing the torpedo tubes to fall into the engine room and crushed the watch below.

Immediately MOHAWK started to sink. All remaining hands were called to deck. Within a minute, she was listing heavy to port, rolling over until she lay on her side. There was no time to launch lifeboats but six 'Carleys' managed to float clear. Most of the crew were left in the water as MOHAWK sank. Her stern touched the bottom with her fo'c'sle above the surface. Survivors were picked up by NUBIAN while JANUS was ordered to sink the dying destroyer by firing 4.7 inch shells into her fo'c'sle. MOHAWK slipped beneath the surface and 41 men were lost with her.