Portland accompanied the invasion fleet to Guadalcanal, escorting Enterprise.
She remained off the coast protecting the landings at Tulagi and Guadalcanal from 7–9 August.
In this duty, she missed the Battle of Savo Island and withdrew two days later following Enterprise.
She then remained in the area to support the Guadalcanal operations and to protect communications lines for the attacking forces.

Remaining with Enterprise, she later participated in the Battle of the Eastern Solomons.
On 24 August she was posted to air defense to the port of Enterprise, and though she and her sisters were able to down a number of Japanese aircraft, the carrier was hit at 18:34.
She continued to protect the carrier through 25 August, when Allied forces prevented reinforcement of Japanese units in the Solomons by a large naval armada under Admiral Isoroku Yamamoto.
Following the battle she escorted Enterprise to Pearl Harbor and was then ordered on a secret mission to the Gilbert Islands to conduct a raid on Tarawa with light cruiser San Juan.
She took aboard Rear Admiral Mahlon S. Tisdale and was designated Task Unit 16.9.1.
Between 14:10 and 14:51 on 15 October she attacked Japanese ships near the island, damaging a transport and a destroyer and suffering one damaged aircraft before she withdrew and rejoined the Enterprise task group near the Solomons.

She then steamed south to take part in the Battle of the Santa Cruz Islands as one of the escorts for Enterprise.
The carrier came under heavy air attack at 10:12 on 24 October, and Portland suffered her first wartime damage as one of her 1.1-inch (28 mm) guns exploded in firing and again when one of her AA guns depressed too low and damaged the splinter shield, injuring 19 officers and enlisted men.
In heavy fighting Enterprise was hit once but Portland and the task group shot down several aircraft.
At 11:53 the bridge lost control of steering, and before it could regain control, a Japanese submarine was spotted.
The submarine struck Portland with three torpedoes, but none detonated, likely because the submarine had fired too close and they had no time to arm.

Two weeks later, she participated in the Naval Battle of Guadalcanal from 12–15 November, which resulted in heavy damage to both forces but broke up the determined Japanese effort to disrupt the landing of 6,000 American troops on Guadalcanal, to bombard Henderson Field, and to land 7,000 reinforcements of their own.
At the outbreak of the battle, Portland was escorting a convoy traveling to Guadalcanal from New Caledonia as part of Task Force 67.
After a four-day journey they arrived and began to offload supplies on 12 November and were countered by a Japanese air attack of 46 aircraft.
That night, she was among a force of five cruisers and eight destroyers under Daniel J. Callaghan which steamed to counter an approaching Japanese force.
They spotted a Japanese force of two battleships, one cruiser and eleven destroyers and immediately opened fire, sinking the Japanese destroyer Akatsuki.
Shortly thereafter, Portland was struck by a torpedo fired by either the destroyer Inazuma or the destroyer Ikazuchi at 01:58, causing heavy damage to her stern.
The torpedo struck the starboard side, which blew off both inboard propellers, jammed the rudder five degrees to starboard, and jammed her Number Three turret in train and elevation.
A four degree list was quickly corrected by shifting ballast, but the steering problem could not be overcome and the ship was forced to steam in circles to starboard.
The blast disrupted her steering column, forcing her to steer in a circle.
At the end of her first circle, she fired on the battleship Hiei, with her forward turrets.
The Japanese ship returned fire, but all salvos passed over the cruiser.
In the four six-gun salvos returned by Portland, she succeeded in starting fires in the Japanese ship.
 At dawn, she was one of three U.S. ships still too damaged to withdraw on her own power.
Then again at 06:30, still circling, Portland opened fire on the abandoned hulk of the destroyer Yūdachi at a range
Portland accompanied the invasion fleet to Guadalcanal, escorting Enterprise. She remained off the coast protecting the landings at Tulagi and Guadalcanal from 7–9 August. In this duty, she missed the Battle of Savo Island and withdrew two days later following Enterprise. She then remained in the area to support the Guadalcanal operations and to protect communications lines for the attacking forces.
Remaining with Enterprise, she later participated in the Battle of the Eastern Solomons. On 24 August she was posted to air defense to the port of Enterprise, and though she and her sisters were able to down a number of Japanese aircraft, the carrier was hit at 18:34. She continued to protect the carrier through 25 August, when Allied forces prevented reinforcement of Japanese units in the Solomons by a large naval armada under Admiral Isoroku Yamamoto. Following the battle she escorted Enterprise to Pearl Harbor and was then ordered on a secret mission to the Gilbert Islands to conduct a raid on Tarawa with light cruiser San Juan. She took aboard Rear Admiral Mahlon S. Tisdale and was designated Task Unit 16.9.1. Between 14:10 and 14:51 on 15 October she attacked Japanese ships near the island, damaging a transport and a destroyer and suffering one damaged aircraft before she withdrew and rejoined the Enterprise task group near the Solomons.
She then steamed south to take part in the Battle of the Santa Cruz Islands as one of the escorts for Enterprise. The carrier came under heavy air attack at 10:12 on 24 October, and Portland suffered her first wartime damage as one of her 1.1-inch (28 mm) guns exploded in firing and again when one of her AA guns depressed too low and damaged the splinter shield, injuring 19 officers and enlisted men. In heavy fighting Enterprise was hit once but Portland and the task group shot down several aircraft. At 11:53 the bridge lost control of steering, and before it could regain control, a Japanese submarine was spotted. The submarine struck Portland with three torpedoes, but none detonated, likely because the submarine had fired too close and they had no time to arm.
Two weeks later, she participated in the Naval Battle of Guadalcanal from 12–15 November, which resulted in heavy damage to both forces but broke up the determined Japanese effort to disrupt the landing of 6,000 American troops on Guadalcanal, to bombard Henderson Field, and to land 7,000 reinforcements of their own. At the outbreak of the battle, Portland was escorting a convoy traveling to Guadalcanal from New Caledonia as part of Task Force 67. After a four-day journey they arrived and began to offload supplies on 12 November and were countered by a Japanese air attack of 46 aircraft. That night, she was among a force of five cruisers and eight destroyers under Daniel J. Callaghan which steamed to counter an approaching Japanese force. They spotted a Japanese force of two battleships, one cruiser and eleven destroyers and immediately opened fire, sinking the Japanese destroyer Akatsuki. Shortly thereafter, Portland was struck by a torpedo fired by either the destroyer Inazuma or the destroyer Ikazuchi at 01:58, causing heavy damage to her stern. The torpedo struck the starboard side, which blew off both inboard propellers, jammed the rudder five degrees to starboard, and jammed her Number Three turret in train and elevation. A four degree list was quickly corrected by shifting ballast, but the steering problem could not be overcome and the ship was forced to steam in circles to starboard. The blast disrupted her steering column, forcing her to steer in a circle. At the end of her first circle, she fired on the battleship Hiei, with her forward turrets. The Japanese ship returned fire, but all salvos passed over the cruiser. In the four six-gun salvos returned by Portland, she succeeded in starting fires in the Japanese ship.  At dawn, she was one of three U.S. ships still too damaged to withdraw on her own power. Then again at 06:30, still circling, Portland opened fire on the abandoned hulk of the destroyer Yūdachi at a range 
USS Portland (CA-33)