Portland was assigned after completion to CruDiv 4, with the Scouting Force, but joined CruDiv 6 the following year. She had a spell with CruDiv 5 in 1935, then with CruDiv 6 in 1936 before once again being assigned to CruDiv 5. She remained with this division until the end of 1940, when she was reassigned to CruDiv 4 for the whole of the war period. In December 1941 she was attached to TF11, covering the transport of Marine aircraft by Lexington to Midway Island, and was then involved in abortive attempts to relieve Wake Island with the same task force. In May 1942 she was involved in the Battle of the Coral Sea as a unit of TF17, when she rescued survivors from Lexington. The following month she participated in the Battle of Midway, and by August had been committed to the Guadalcanal campaign, for the landings on that island and Tulagi, now attached to TF16. At the Battle of the Eastern Solomons, towards the end of August, she was with TF61. On 16 October Portland sailed with Enterprise and TF61 to intercept Japanese forces heading for the eastern Solomons, which culminated in the Battle of Santa Cruz, when the cruiser was lucky to survive hits by three aircraft torpedoes, none of which exploded. However, in November she was deployed to escort troop reinforcements from Noumea to Guadalcanal, and in the subsequent battle off that island on 13 November was hit aft by a shallow-running torpedo, which sheared off both inboard screws. Her after turret was disabled, but the cruiser managed to sink the destroyer Yudachi in the engagement. She returned to the USA via Tulagi, Sydney and Pearl Harbor for repair at Mare Island. The work was completed by the beginning of March 1943, after which she was deployed to the Aleutians for the bombardment of Kiska. Portland returned to the South Pacific to operate in the Marshall and Gilbert Islands at the end of 1943, then supported operations at Hollandia in April 1944. Refitted again at Mare Island over the summer of 1944, the ship then joined the Fire Support Group for the landings on Peleliu in mid-September. In October she participated in the landings at Leyte, and in the subsequent Battle of the Surigao Straits. The year 1945 saw her in action at Lingayen Gulf, Corregidor and Okinawa, as well as accepting the surrender of Japanese forces at Truk in the Carolines in September. Her last tasks were Magic Carpet cruises to bring home US servicemen, before paying off on 12 July 1946. Stricken on 1 March 1959 after spending the intervening years in reserve, she was sold to Union Mineral and Alloys Corp., New York, on 6 October 1959 and broken up at Panama City from December.

Indianapolis assumed the role of Flagship, Scouting Force, from November 1933, and remained in the capacity of flagship throughout her career, latterly as Flagship Cruisers, Pacific Fleet and CruDiv 4. On 7 December 1941 she was assigned to TF12, but joined TF11 at Pearl Harbor on 13 December. Early in 1942 she operated in the South Pacific and New Guinea, screening the carriers Lexington and Saratoga. A refit at Mare Island occupied much of April to July, after which she was employed on escort tasks as far afield as Australia and the Aleutians. In August 1942 she bombarded Kiska, and in the Aleutians in February 1943 sunk an ammunition ship, then remained in the Aleutians until the summer of 1943, when she returned to Mare Island for refit. On her return to service she assumed the role of Flagship, 5th Fleet, at Pearl Harbor in October, and during the following month participated in the invasion of the Gilbert Islands, bombarding Tarawa and Makin. At the beginning of 1944 she moved to the Marshall Islands, bombarding Kwajalein. In the ensuing months she saw action at Saipan, in the Battle of the Philippine Sea, at Tinian, at Guam and in the Carolines. Another refit was carried out at Mare Island between November 1944 and January 1945, before she returned to service off Iwo Jima and then escorted the carriers in raids on the Japanese islands. On 31 March, off Okinawa, she was hit by kamikaze aircraft aft, suffering damage to her shafts that needed repair in the USA. This was carried out between June and July at Mare Island, after which she was detailed to ferry components of the first atomic bomb to Tinian. She arrived at Tinian on 26 July 1945, disembarked the bomb components, then sailed for Leyte via Guam. Having left Guam on 28 July the ship proceeded towards Leyte, but some 600nm south west of Guam and 550nm north-east of Leyte she was hit by three torpedoes from the submarine I 58 and sank with heavy casualties. As she was not reported overdue for several days, the losses among her crew were greatly increased.