Eskimo's journeys around the world ranged from the Arctic Circle to the Indian Ocean. In January 1939, a month after her commissioning, she took part in the combined Home and Mediterranean Fleet Exercises off Gibraltar. On 17th May, a 2 pounder gun was being cleaned when a blank charge in the breech suddenly went off. No one in the immediate vicinity was injured but nearby, two men were lowering the motor-boat and two more were working on a hawser. One person was killed and the other three injured. Like the other Tribals, Eskimo had trouble with her turbines and was sent for refit in September 1939. Soon she was back at Scapa Flow and while in company with HMS Ashanti, the German air force attacked for the first time on 17th October. Eskimo shot down one aircraft and later came to the assistance of the damaged former battleship Iron Duke.

The winter of 1939/40 consisted of patrols, convoy duty and high speed steaming in rough weather. After a refit was completed in March 1940, Eskimo was ready to participate in the impending operations in Norwegian waters. During the Second Battle of Narvik, Eskimo had her bows blown off by a torpedo. She limped back to Skilfiord, Norway for temporary repairs. Surviving aerial bomb attacks, she was finally made ready for sea on 31 May 1940. The destroyer proceeded without incident, to the Vickers-Armstrong yard at Newcastle-on-Tyne, England for a rebuild. By September 1940, the work was completed and Eskimo re-joined the 6th Destroyer Flotilla (6th D.F.).

During the winter or 1940/41, the Flotilla was mainly engaged in the escort of the big ships of the Home Fleet. In June 1941, the destroyer was in need of refit so she was dispatched to Green and Silley Weir in London. On returning to the 6th D.F. in September 1941, she paired up with HMS Ashanti in order to support Home Operations during the coming winter.

In March 1942, Eskimo took part in the movements which screened convoys PQ-8 and PQ-12 and in the abortive sweep to intercept the German battleship Tirpitz. After a refit in Falsmouth England, HMS Eskimo rejoined HMS Ashanti and they took part in the Pedestal convoy to Malta. Under Captain Eaton, Eskimo became leader of Force 'H' destroyer screen in order to support the Allied landings in North Africa in November 1942. Once the assault was over, the destroyers were employed for various coastal activities.

In January 1943, HMS Eskimo was laying alongside HMS Nelson preparing for sea when a fire broke out in one of Eskimo's boiler rooms. Damage was chiefly confined to the main electric cable runs and it took a week to repair the damage.

By the 8th of May, the Axis armies in North Africa were defeated and Eskimo took part in Operation Retribution, the effort to sink, burn or destroy enemy vessels passing through the Sicilian Narrows. In July, while participating in Operation Husky, she was attacked by German dive bombers. A small bomb hit the port side abreast of 'X' gun mounting and penetrated No. 5 and 6 fuel oil tanks. The explosion wrecked the Gear Room, started a fire and killed or injured 19 men. Within 40 minutes, the fire was put out and HMS Tartar took HMS Eskimo in tow. Escorted by the Greek escort destroyer Miaoulis, the ships reached Malta and temporary repairs were started. Since one of Eskimo's propellor shafts was buckled, it was agreed that she should return to the U.K. using one propellor only. The destroyer arrived at Immington, England in September in order to begin her refit. Besides repairing battle damage, a lattice foremast replaced the tripod and 20mm Oerlikons were fitted to replace the 0.5" machine guns.

By April 6th 1944, HMS Eskimo completed her sea trials and left for Scapa Flow. Her exercises were uneventful and by May, she was assigned to the 10th Destroyer Flotilla based at Plymouth, England. HMS Eskimo took part in the exercises preceding D-Day, the Tunnel anti- shipping sweeps and the Hostile Operation covering minelayers. She shared the Hurd Deep patrol with HMS Ashanti and the rest of her assignments were with the 10th D.F. from June 1944 onwards.

During the evening of June 24 between 1600 and 1900hours, HMS Eskimo and HMCS Haida depth-charged the German submarine U-971 in the English Channel. On the ninth attack, the submarine broke surface and Eskimo opened fire with all of her guns. Haida started firing her 'B' mounting and Oerlikons. As a result, U-971's conning tower was destroyed and the submarine caught fire. A boarding party was successful in seizing confidential code books before the sub suddenly slid below the surface.

On the next patrol which took place on 27/28 June, a 3" shell fired from a German trawler hit Eskimo in No 1 Boiler Room. She lost all steam and electric power, but continued to fire while HMCS Huron circled her with smoke. Eskimo managed to steam back to Plymouth at 20 knots using only one boiler.

As the winter of 1944 approached, there was little work for Tribals in Home waters, so it was decided to send them to the Far East to join the Australian Tribals in the final defeat of Japan. She left for the Indian Ocean by way of the Mediterranean but it was soon realized that the Tribals had been 'arcticized' so they could operate in freezing temperatures. In the Tropics, the temperature in the galley could reach 160 degrees, and no ship ever received water coolers. Eskimo was refitted to make her more hospitable for work in hot, humid, climates. For most of the spring of 1945, she was employed in operations south of Ramree Island (Burma) where odd parties of Japanese were holding out.

Eskimo and other Tribals later joined up with Force 61 to intercept and destroy what was left of the Japanese surface fleet. She was also included in the force which covered minesweeping operations in the Nicobar Islands (south of Burma) from 5th - 11th July 1945. Prior to the end of the war it was decided to send the destroyer to Durban, South Africa for a refit, solely for the purposes of keeping the work force employed. The Eskimos did not think their ship was in need of a refit but their objections were overruled and the ship proceeded to Durban. En route, Eskimo heard about V-J day.

By November 1945, the refit was over and she sailed for home. Eskimo arrived back in England on the Friday before Christmas. Early in 1946, her torpedo tubes were removed and a type of prefabricated house was placed on her deck. Her screws were removed to prevent her from touching bottom, then she was towed to Queensborough, England. Eskimo ended her days as an accommodation and headquarters ship for minesweepers, wreck-disposal vessels, salvage craft which were clearing the Thames and Medway estuaries. She was then laid up, first at Sheerness, then at Harwich and finally used as a target in the Gareloch. On 27 June 1949, Eskimo was sold for scrapping at Troon.