North Carolina and the Navy began the long island-hopping campaign for victory over the Japanese by landing marines on Guadalcanal and Tulagi 7 August 1942. After screening Enterprise (CV -6 ) in the Air Support Force for the invasion North Carolina guarded the carrier during operations protecting supply and ammunition lines southeast of the Solomons. Enemy carriers were located 24 August, and the Battle of the Eastern Solomons erupted. The Americans struck first, sinking carrier Ryujo; Japanese retaliation came as bombers and torpedo planes, covered by fighters, roared in on Enterprise and North Carolina. In an 8 minute action, North Carolina shot down between 7 and 14 enemy aircraft, her gunners standing to their guns despite the jarring detonation of 7 near-misses. One man was killed by a strafer, but the ship was undamaged. The protection North Carolina could offer Enterprise was limited as the speedy carrier drew ahead of her. Enterprise took three direct hits while her aircraft severely damaged sea-plane carrier Chitose and hit other Japanese ships. Since the Japanese lost about 100 aircraft in this action, the United States won control of the air and averted a threatened Japanese reinforcement of Guadalcanal.

North Carolina now gave her mighty strength to protect Saratoga (CV-3). Twice during the following weeks of support to marines ashore on Guadalcanal, North Carolina was attacked by Japanese submarines. On 6 September, she maneuvered successfully, dodging a torpedo which passed 300 yards off the port beam. Nine days later, sailing with Hornet (CV-8), North Carolina took a torpedo portside, 20 feet below her waterline, and 5 of her men were killed. But skillful damage control by her crew and the excellence of her construction prevented disaster; a 5.5 degree list was righted in as many minutes, and she maintained her station in a formation at 25 knots.