Her first major wartime operation was the rescue of a submarine. In September 1939, the submarine HMS SPEARFISH was severely damaged by enemy action while operating in the German Bight. MASHONA, HMS MATABELE and HMS SOMALI successfully located the crippled sub on 25th/26th September. The force withdrew from enemy waters and SPEARFISH was escorted back to England without incident. In March 1940, MASHONA completed a refit at Chatham and her timely return to Scapa Flow, Scotland allowed her to join another Norwegian convoy. When Norway was invaded, MASHONA was one of the first destroyers on the scene and the Tribal helped to round up various merchant ships and escort them across the North Sea to England.

By the end of April, the land campaign in central Norway was going badly for the Allies and the decision was made to withdraw. MASHONA and three of her sister Tribals joined the force which was sent to evacuate the troops south of Trondheim, Norway. Further north, operations were still being conducted against Narvik and the Allies were still planning to capture the port city. Troop convoys had to be escorted to Harstad, the advance base for the assault force. MASHONA shared in this work and screening the aircraft carrier HMS ARK ROYAL. Soon after Narvik was captured, it had to be evacuated, so the Tribal would become part of the sea force which would provide screening for the outbound troop ships. On 6th June 1940, MASHONA and other ships left Scapa Flow to execute this mission. Aside from escorting the evacuation convoys, the force also hunted, without success, for the German battlecruisers SCHARNHORST and GNEISNAU.

On 20th June, MASHONA found herself in a cauldron of mountainous waves. She hit one of these rogue waves and fell to the bottom of the trough with such force that her bottom plating was weakened. It was the first time that Commander Selby had to shore up the plating in a downward direction to prevent it from crumbling. Arriving in Rosyth, England on 27th June, the ship was dry-docked and it was discovered that 240 rivets had to be tightened. After more patrols with HMS TARTAR and HMS BEDOUIN, MASHONA arrived at Liverpool for refit in August 1940. There, she was inspected by King George VI and Queen Elizabeth. The refit was completed on 5th October and for the rest of 1940, MASHONA was employed on patrols and convoy escort in the Western approaches, especially northwest of Ireland. One of her tasks involved rescuing survivors from the passenger liner ROTORUA, torpedoed on 11th December.

One dark night in January 1941, emergency sailing orders were received while the destroyer was berthed in Gutter Sound at Scapa Flow. The signal did not specify which boom gate to use as an exit. In the ensuing confusion, MASHONA collided with HMS SIKH that was moored at a buoy near a floating dock. One officer in SIKH found himself to be an unwilling captive in his quarters because MASHONA'S bow had sliced through the middle of his cabin and formed a barrier between his bunk and the cabin door! He had to wait there until the ships were separated. Repairs to MASHONA were completed at Hartlepool England on 3rd March. After a number of sweeps and patrols in the Atlantic, she joined other ships of the Home Fleet in the search for the German battleship BISMARCK.

During the pursuit, several of the Tribals including MASHONA ran low on fuel and were ordered back to base. While in company with TARTAR on 27th May 1941, German aircraft commenced bombing attacks on the two ships. One bomb found its mark and struck MASHONA'S port side, abreast of the forefunnel. It penetrated No.1 Boiler Room and exploded there, blowing a huge hole in the side of the ship. The air attack continued. As MASHONA continued listing to port, her guns were hand trained to starboard. At least the crew would be able to fire at any target that passed overhead. To lighten the Tribal, all unnecessary gear was thrown overboard for a 45 minute interval but it was to no avail. MASHONA was listing farther and farther with each roll. Orders were given to abandon ship.

For an hour, there was a lull in the bombing. This gave TARTAR an opportunity to pick up the survivors. Forty-six men had been lost in the action. The Tribal was now on her side and refusing to sink. TARTAR fired a torpedo and missed. By this time, HMS SHERWOOD and HMS ST CLAIR had arrived and they were ordered to fire at the hull. The shells hit, the trapped air rushed out and MASHONA slipped into the sea. MASHONA'S battle ensign was saved and now resides in the Cathedral of Salisbury, Southern Rhodesia.