Duncan sailed from New York on 20 June 1942 for the South Pacific, arrived at Espiritu Santo on 14 September to join TFs 17 and 18, and with them departed the same day to cover transports carrying the 7th Marine Regiment to reinforce Guadalcanal. Duncan was in the screen of the aircraft carrierWasp next day when the task force was attacked by two Japanese submarines. Wasp was torpedoed, and so severely damaged that she had to be sunk by United States ships. Duncan picked up survivors from the carrier, transferring 701 officers and men to other ships, and 18 wounded and two bodies to the base hospital at Espiritu Santo upon her arrival 16 September.
Duncan continued to operate from Espiritu Santo to the Solomons, screening transports and ships of the covering forces. On 11 October 1942, she was in the screen of Task Force 64 (TF 64) which was assigned to protect a vital transport convoy carrying reinforcements to Guadalcanal. Contact was made with a large enemy surface force just as the American ships were executing a course change as part of their battle plan. Duncan, having a clear radar contact and seeing her flagship apparently steady upon a course which would close the target, believed the destroyers were closing to attack, and found herself charging alone toward the enemy force.
In the resulting Battle of Cape Esperance, Duncan hit a cruiser with several salvos, then shifted fire to a destroyer, at the same time maneuvering radically to avoid enemy fire and that from her own forces, who were now joining in the attack. She got off two torpedoes toward her first target, Furutaka, and kept firing until hits she had received put her out of action. The commanding officer, Lieutenant Commander Edmund B. Taylor who was awarded the Navy Cross for his actions in this battle ordered the bridge, isolated by fire, abandoned, and the wounded lowered into life rafts. The men on board attempted to beach the ship on Savo Island, but then, believing she might yet be saved, continued to fight the fires until power failed, when they abandoned ship. Destroyer McCalla rescued 195 men from the shark-infested waters and made an attempt to salvage Duncan, but she sank on 12 October 1942, about 6 nautical miles (11 km; 6.9 mi) north of Savo Island.
Awards
Duncan received one battle star for World War II service.