Sighted by the enemy who reported them as one battleship, one cruiser, and four destroyers the American warships spent most of the day on the 14th avoiding contact with enemy planes. From the information available in dispatches, the commander of the American task force, Rear Admiral Willis Augustus Lee, knew of the presence of three groups of enemy ships in the area, one of which was formed around at least two battleships. Proceeding through the flat claim sea and disposed in column formation with Walke leading, the American ships approached on a northerly course about nine miles west of Guadalcanal.

Lee's ships continued making their passage, picking up Japanese voice transmissions on the radio while the ships radar scanned the darkness. At 0006 on 15 November, USS Washington received a report that indicated the presence of three ships, rounding the north end of Savo Island, headed westward. Almost simultaneously the flagship's radar picked up two ships on the same bearing.

Ten minutes later, Washington opened fire with her 16-inch guns; and, within seconds, South Dakota followed suit. Walke opened fire at 0026, maintaining a rapid barrage at the Japanese light cruiser Nagara. After checking fire within a few minutes, the lead destroyer opened up again at a Japanese destroyer 7,500 yards to starboard and, later, at gunflashes off her port side near Guadalcanal.

Japanese shells straddled Walke twice, and then a Long Lance torpedo slammed into her starboard. Almost simultaneously, a salvo of shells from one of the Japanese light cruisers hurtled down upon the hapless destroyer, a deluge of steel that struck home with devastating effect in the radio room, the foremast, below the gig davits and on the after deckhouse. Meanwhile the torpedo had blown off the bow of the ship; and fire broke out as a forward magazine blew up.

With the situation hopeless, Comdr Thomas Edward Fraser, Walke's commanding officer, ordered the ship abandoned. As the destroyer sank rapidly by the bow, only two life rafts could be launched. The others had been damaged irreparably. After the crew made sure that the depth charges were set on safe, they went over the side just before the ship slipped swiftly under the surface.

As Washington dueling with the Japanese battleship Kirishima and smaller ships swept through the flotsam and jetsam of battle, she briefly noted Walke's plight and that of Preston, which had also gone down under in a deluge of shells. At 0041 just a minute or so before Walke's battered form sank beneath the waves of the waters off Savo Island into "Ironbottom Sound" life rafts from the battleship splashed into the sea for the benefit of the survivors. Although the destroyer's depth charges had apparently been set to "safe," some depth charges went off, killing a number of swimming survivors and seriously injuring others. As the battle went on ahead of them, the able-bodied survivors placed their more seriously wounded comrades on rafts.

Walke's survivors were, at one point, in two groups some clinging to the still floating bow section and others clustered around the two rafts that ship had been able to launch. During the harrowing night, they were twice illuminated by enemy warships but not molested, before the enemy switched off his searchlights and moved on.

At dawn, however, Walke's survivors and those from Preston witnessed the end of a quartet of Japanese transports beached during the night. Bombed and strafed by Army, Marine, and Navy planes including aircraft from USS Enterprise (CV-6) the four Japanese ships received the coup de grace from USS Meade (DD-602) that morning, just before the destroyer altered course and picked up the destroyer's men from Walke and Preston.

Meade rescued 151 men from Walke,55 were wounded though six of whom later died after they were brought ashore at Tulagi. Six officers including Comdr Thomas Edward Fraser and 69 men had died in the ship's fiery end off Savo Island. She was struck from the Navy list on 13 January 1943.