On 7 December 1941, Louisville, escorting A. T. Scott and President Coolidge, was en route from Tarakan, East Borneo, to Pearl Harbor.
She continued on to Hawaii, stopped briefly to survey the damage and proceeded on to California.
There she joined Task Force 17 (TF 17) and steamed from San Diego on 6 January 1942, for Samoa, landing troops there on 22 January.
Her first offensive operation of the war came on her return trip when she took part in carrier plane raids on 1–2 February on the Gilbert and Marshall Islands.
During this action, one of her scout planes went missing and the pilot and aircrewman were lost.

After a short stay at Pearl Harbor, Louisville commenced patrolling the Ellice Islands area to help protect American bases in that vicinity.
Early in March she joined TF 119, a carrier force, and began operations to stem the Japanese advance down the Bismarck Archipelago and the Solomons.
This force steamed in the Salamaua-Lae-Rabaul sector for a number of days, making airstrikes on numerous objectives.

Following this operation, Louisville returned to Pearl Harbor, proceeding from there to Mare Island Navy Yard, San Francisco, where her anti-aircraft armament was increased with additional 1.1 in and 20 mm cannon fitted.
On 31 May, she steamed for the Aleutians to join TF 8 to counter the enemy forces expected to be in the area.
 Fortunately for Louisville, the Japanese carrier force did not locate her and the other cruisers during the attacks on Dutch Harbor, which coincided with the Battle of Midway.
 Her duties, during this period of Japan's strongest efforts to establish the northern end of her "ribbon defense" in the western Aleutians, were primarily those of convoy escort, but included shore bombardment of Kiska Island.

On 11 November, the cruiser departed San Francisco for Pearl Harbor, continuing, after a few days on to the South Pacific, escorting several troop transports as far as New Caledonia.
She then proceeded north to Espiritu Santo to Join TF 67, which was then battling Japanese forces in the Solomons.
On 29 January 1943, Louisville participated In the Battle off Rennell Island, the last of the seven naval battles for Guadalcanal, after which she operated east of the island until it was entirely secured.

In April, Louisville steamed, via Pearl Harbor, to the Aleutians.
There, as a unit of TF 16, the cruiser covered the assault and occupation of Attu (11–30 May) and participated In the pre-invasion bombardment of Kiska in July.

After the latter was evacuated by the Japanese, she conducted escort of convoy operations in the northern Pacific.
In August 1943 she proceeded to the Mare Island Navy Yard for an overhaul to her machinery and alterations.
Louisville was in overhaul at Mare Island from 8 October until 24 December 1943.
Like her sister ships her forward mast was cut down and her aft mainmast was removed and replaced with a lighter tripod just aft of the second funnel.
Louisville had the camouflage measure 32-6D paint scheme added and two new mark 34 main battery directors installed.
The 1.1 in AA cannon mounts were removed and replaced with several quad 40 mm Bofors mounts along with numerous 20 mm cannon.
Improved radars and flagship spaces were also added.
Following this work in January 1944, Louisville returned to the southern Pacific as the flagship of Rear Admiral J. B. Oldendorf, who was to command the naval gunfire support groups through the amphibious operations ahead.
In the Marshalls at the end of the month, she bombarded Wotje Atoll, west of Kwajalein, on 29 January.
Then the cruiser turned her guns on the airfield and troop concentrations on Roi and Namur on the southern tip of the atoll, contributing to the conquest of those islands by 3 February.
During this campaign, while waiting bombardment further targets an 8-inch 55 caliber shell fired from USS Indianapolis ricocheted off the island to explode a near miss alongside Louisville starboard side causing heavy pieces of shrapnel which damaged the chiefs quarters, pierced the bulkhead, and turret No.
3 – 8-inch gun had shrapnel d
On 7 December 1941, Louisville, escorting A. T. Scott and President Coolidge, was en route from Tarakan, East Borneo, to Pearl Harbor. She continued on to Hawaii, stopped briefly to survey the damage and proceeded on to California. There she joined Task Force 17 (TF 17) and steamed from San Diego on 6 January 1942, for Samoa, landing troops there on 22 January. Her first offensive operation of the war came on her return trip when she took part in carrier plane raids on 1–2 February on the Gilbert and Marshall Islands. During this action, one of her scout planes went missing and the pilot and aircrewman were lost.
After a short stay at Pearl Harbor, Louisville commenced patrolling the Ellice Islands area to help protect American bases in that vicinity. Early in March she joined TF 119, a carrier force, and began operations to stem the Japanese advance down the Bismarck Archipelago and the Solomons. This force steamed in the Salamaua-Lae-Rabaul sector for a number of days, making airstrikes on numerous objectives.
Following this operation, Louisville returned to Pearl Harbor, proceeding from there to Mare Island Navy Yard, San Francisco, where her anti-aircraft armament was increased with additional 1.1 in and 20 mm cannon fitted. On 31 May, she steamed for the Aleutians to join TF 8 to counter the enemy forces expected to be in the area.  Fortunately for Louisville, the Japanese carrier force did not locate her and the other cruisers during the attacks on Dutch Harbor, which coincided with the Battle of Midway.  Her duties, during this period of Japan's strongest efforts to establish the northern end of her "ribbon defense" in the western Aleutians, were primarily those of convoy escort, but included shore bombardment of Kiska Island.
On 11 November, the cruiser departed San Francisco for Pearl Harbor, continuing, after a few days on to the South Pacific, escorting several troop transports as far as New Caledonia. She then proceeded north to Espiritu Santo to Join TF 67, which was then battling Japanese forces in the Solomons. On 29 January 1943, Louisville participated In the Battle off Rennell Island, the last of the seven naval battles for Guadalcanal, after which she operated east of the island until it was entirely secured.
In April, Louisville steamed, via Pearl Harbor, to the Aleutians. There, as a unit of TF 16, the cruiser covered the assault and occupation of Attu (11–30 May) and participated In the pre-invasion bombardment of Kiska in July.
After the latter was evacuated by the Japanese, she conducted escort of convoy operations in the northern Pacific. In August 1943 she proceeded to the Mare Island Navy Yard for an overhaul to her machinery and alterations. Louisville was in overhaul at Mare Island from 8 October until 24 December 1943. Like her sister ships her forward mast was cut down and her aft mainmast was removed and replaced with a lighter tripod just aft of the second funnel. Louisville had the camouflage measure 32-6D paint scheme added and two new mark 34 main battery directors installed. The 1.1 in AA cannon mounts were removed and replaced with several quad 40 mm Bofors mounts along with numerous 20 mm cannon. Improved radars and flagship spaces were also added. Following this work in January 1944, Louisville returned to the southern Pacific as the flagship of Rear Admiral J. B. Oldendorf, who was to command the naval gunfire support groups through the amphibious operations ahead. In the Marshalls at the end of the month, she bombarded Wotje Atoll, west of Kwajalein, on 29 January. Then the cruiser turned her guns on the airfield and troop concentrations on Roi and Namur on the southern tip of the atoll, contributing to the conquest of those islands by 3 February. During this campaign, while waiting bombardment further targets an 8-inch 55 caliber shell fired from USS Indianapolis ricocheted off the island to explode a near miss alongside Louisville starboard side causing heavy pieces of shrapnel which damaged the chiefs quarters, pierced the bulkhead, and turret No. 3 – 8-inch gun had shrapnel d
USS Louisville (CA-28)