Launched on 20 August 1944, she was sponsored by Mrs. Edward J. Kelly, wife of the Mayor of Chicago, Illinois, and commissioned at the Philadelphia Navy Yard on 10 January 1945, Captain Richard R. Hartung, USN, in command.

Designed to operate offensively with strike and amphibious forces, Chicago spent her transit time conducting various anti-air drills, gunnery exercises, and radar tracking training.

Underway that same day, with the destroyer Stockham, added for anti-submarine screen, the ships joined Rear Admiral Radford's Task Group 38.4 north of the Mariana Islands on 8 July.

Added to the anti-aircraft screen, Chicago guarded the Task Group's carriers as they conducted air strikes against the Tokyo Plains area, Honshū, Japan, on 10 July.

After refueling on 12 July, the Task Group returned to the Japanese coast and launched air strikes against airfields, shipping, and railways in the northern Honshū and Hokkaidō areas the next day.

After replenishment operations on 16 July, the cruiser resumed screening the carriers as they launched air strikes over the Tokyo Plains, northern Honshū and Hokkaidō, and the Kure-Kobe area over the next two weeks.

Designed to provide long-range air, surface, and sub-surface defense for task forces, Chicago was recommissioned at the San Francisco Naval Shipyard on 2 May 1964, and was assigned to Cruiser-Destroyer Flotilla Nine of the US Pacific Fleet.

During fleet exercise "Hot Stove" in August–September, Chicago practiced anti-air and ASW operations, including firing ASROC and tube-launched torpedoes against submerged "enemy" submarines.

After a cruise to Hawaii from 19 October to 3 November, during which the cruiser practiced tactical data sharing training with the aircraft carrier Kitty Hawk and destroyer Mahan, the ship finished out the year conducting tests and exercises in the San Diego area.

In April, the warship participated in Exercise "Gray Ghost," where the cruiser operated as tactical flagship for the anti-air warfare commander, Rear Admiral Elmo R. Zumwalt, Jr. On 12 May 1966, Chicago got underway for her first Vietnam deployment.

From 15 June to 13 July, Chicago, call-sign Red Crown, began evaluating the concept of radar surveillance of all U.S. Navy air operations over designated areas of the Gulf and North Vietnam.

On her second PIRAZ tour, from 29 July to 11 August, Chicago assumed the duties of anti-air warfare commander for short periods of time and demonstrated the ability of a CG to track complex air operations.

Underway for such widely divergent responsibilities as providing guest cruises for the Secretary of the Navy, serving as First Fleet flagship, and air warfare exercises with USS Constellation, the cruiser spent the first five months of the year off California.

After another fleet exercise in July, where Chicago's Talos battery scored a direct hit on a drone at a range of 96 miles, the cruiser spent August conducting official visits to Seattle, Washington, Vancouver, and Esquimalt, British Columbia.

Arriving on station in the Gulf of Tonkin three weeks later, via Yokosuka, Okinawa, and Subic Bay, the ship relieved the cruiser Belknap, beginning PIRAZ duties from 12 November to 14 December.

These responsibilities, improved over the past year, included radar surveillance, coordinating barrier CAP and rescue operations, providing MiG and border warnings, and a wide variety of communication and real-time data sharing services.

After upkeep at Yokosuka, a visit to Hong Kong, and a typhoon evasion, the cruiser returned to the Gulf of Tonkin on 1 August to continue radar surveillance, electronic countermeasures, and missile screen duties.

After a leave and upkeep period, followed by a tender availability that installed Zuni chaff dispensers, the cruiser finished out the year conducting routine inspections, local training exercises, and operations at the missile test range.

After a final readiness test and embarking five guests of the Secretary of the Navy, Chicago departed for another deployment on 6 November 1971 under the command of Captain Thomas William McNamara.

The cruiser monitored all aircraft flying over the gulf, directed friendly CAP, and, despite intense electronic jamming, coordinated fighter escorts during the mid-April B-52 Stratofortress raids against the North Vietnamese.

By maintaining a complete air picture, Chicago vectored damaged bombers around enemy missile sites, set up tanker rendezvous points for planes low on fuel, and directed helicopters on rescue operations.

Chicago and the cruiser Long Beach were given the unusual assignment of protecting A-6 Intruder and A-7 Corsair aircraft mining Hai Phong harbor at low altitude during Operation Pocket Money.

Underway on 13 July, Chicago and her escorts began a monthlong at-sea period, "showing the flag" in the Arabian Sea and the Gulf of Aden, before arriving at Mombassa, Kenya on 9 August.

Following a visit to Hong Kong in early October, the cruiser spent the next month conducting training and fleet exercises in the Philippines area until getting underway for Guam on 17 November.

Technical inspections and equipment modifications, interspersed with a visit by a delegation of French officials, lasted until April when the ship conducted interim refresher training in the southern California operating areas.

Leaving Hong Kong on 31 August, Chicago joined rendezvous with Enterprise for a war-at-sea exercise lasting until 8 September, before returning to Subic for a lengthy upkeep period.

These exercises, including helicopter pad training, simulated missile and torpedo attacks, and other similar drills, continued until 6 September, when the ship got underway for her eighth WestPac tour.

Gunfire exercises, helicopter operations, unreps, and other drills, including a real man overboard rescue on 28 February, lasted until 4 March, when Chicago moored at Manila.

Chicago escorted the aircraft carrier Kitty Hawk and her battle group to Pearl Harbor, conducting exercises with the cruiser Jouett, frigate Lang, and auxiliary vessel Wabash along the way, before steaming on to Subic Bay on 13 June.

While fiscal year 1980 funding for a thorough overhaul and modernization was approved by Congress, an inspection classified the cruiser as unfit for further economical naval service, and on 1 March 1980, Chicago was decommissioned at San Diego.