Two days after he reported, his ship sailed with Task Force (TF) 8 as part of the force covering the movement of marines to Samoa. Detached from TF 8 to provide local cover for the newly arrived forces at Tutuila, San Francisco then rejoined her old division, Cruiser Division 6, part of TF 11, soon after clearing Samoan waters on February 8. Ens. Harris saw his first action on February 20, 1942, when San Francisco screened the aircraft carrier Lexington (CV-2) as TF 11 battled Japanese land-based bombers off Bougainville, in the Northern Solomons. San Francisco received credit for downing one of the attacking aircraft.
On March 10, 1942 , the heavy cruiser stood ready to protect Lexington, as that carrier, and Yorktown (CV-5), launched a successful surprise attack on enemy shipping off the New Guinea settlements of Lae and Salamaua. In the spring of 1942, Ens. Harris' ship escorted convoys between the United States, Hawaii, Australia and the Fiji Islands.
After seeing a convoy safely to Fiji in July, San Francisco joined the expeditionary force bound for the Solomon Islands, in the initial assault phase of "Operation Watchtower", the invasion of Guadalcanal. His ship covered the landings on August 7, and, following a logistics period at Nouméa, New Caledonia, covered a supply convoy to Guadalcanal. During the latter movement, he witnessed the loss of the carrier Wasp (CV-7) on September 15. He took part on the Battle of Cape Esperance on the night of October 11 and 12, and participated in the shelling of Japanese supply and ammunition dumps at Koli Point on November 4.
Commander Herbert E. Schonland, who took command of the heavy cruiser after Captain Cassin Young died of wounds suffered in the Naval Battle of Guadalcanal, praised "the remarkable fire discipline and courage" of Harris and his men. "They met their deaths without flinching," Schonland wrote, "and in a manner which has been an inspiration to us all."
Lt. (jg.) Harris was awarded the Navy Cross posthumously.