After a visit to Salem, Mass., on 4 July 1949, Salem underwent three months of shakedown at Guantanamo Bay, Cuba, between July and October 1949, followed by post-shakedown repairs at the Boston Navy Yard. She then made two cruises to Guantanamo in November and December 1949, and participated in maneuvers with the Atlantic Fleet in early 1950.

Salem departed the east coast on 3 May 1950; and, on 17 May, relieved Newport News (CA-148) as flagship of the 6th Fleet in the Mediterranean. During this, the first of seven deployments to the Mediterranean as fleet flagship, Salem visited ports in Malta, Italy, France, Greece, Turkey, Lebanon, and Algeria, and participated in training exercises. On 22 September, she was relieved by Newport News and returned to the United States.

After three weeks at Boston, Salem joined the Atlantic Fleet for maneuvers; and, on 3 January 1951, sailed for six weeks of intensive gunnery training at Guantanamo. She completed her training off Bermuda; and, on 20 March, sailed for the Mediterranean to relieve Newport News as 6th Fleet flagship. On 19 September, she was relieved by Des Moines (CA-134) and returned to the United States for four months of overhaul at Boston.

Salem sailed on 1 February 1952 for refresher training at Guantanamo and returned to Boston on 29 March for brief repairs. On 19 April, she sailed for her third Mediterranean deployment, relieving Newport News at Algiers on 28 April. Besides the normal port calls and exercises, Salem participated in Exercise "Beehive II," which involved units of the United States, British, Italian, French, and Greek navies. She was relieved once again by Des Moines on 29 September and arrived at Boston on 9 October.

After four months of local operations, Salem sailed for Guantanamo Bay on 24 January 1953 for training. Returning to Boston on 27 February, she sailed for the Mediterranean on 17 April and again relieved Newport News as flagship. Her fourth deployment was marked by Exercise "Weldfest" and by emergency relief work after an earthquake devastated the Ionian Islands. Salem was the first American ship to arrive on the scene, and provided relief supplies and assistance from 13 August until her own stocks ran low four days later. Relieved by Des Moines as flagship on 9 October, she returned to Boston on 24 October and entered the shipyard for overhaul.

On 6 February 1954, Salem sailed again for Guantanamo Bay and returned on 7 April after refresher training. She left Boston on 30 April; and, on arrival in the Mediterranean on 12 May, again assumed duties as 6th Fleet flagship. Relieved by Des Moines at Lisbon on 22 September, she returned to Boston on 29 September. In October and November 1954, she participated in war games with the Atlantic Fleet.

Between 19 January and 22 February 1955, Salem made her annual cruise to Guantanamo Bay for training. After a two-week reserve training cruise, the cruiser sailed for the Mediterranean on 2 May and relieved Newport News on 19 May. During this, her sixth deployment, she participated in a NATO exercise and a Franco-American naval exercise, with Under Secretary of the Navy Thomas S. Gates embarked as observer. Salem departed Barcelona on 23 September and returned to Boston on 2 October 1955 for a four-month overhaul.

The cruiser left Boston on 16 February 1956 for training at Guantanamo in preparation for a 20-month cruise as "permanent" flagship of the Commander, 6th Fleet with homeport at Villefranche-sur-Mer. She returned to Boston on 5 April and sailed for the Mediterranean on 1 May. While she was at sea, the Suez Crisis broke out; and she was diverted to Rhodes in the Eastern Mediterranean where she joined the fleet on 14 May and assumed her flagship duties. She remained in the eastern Mediterranean until mid-June and returned when fighting broke out on 30 October. In April and August 1957, the 6th Fleet, by its presence in the eastern Mediterranean, twice showed United States support for the government of Jordan threatened by subversion. The cruiser departed the Mediterranean on 26 June 1958 and arrived at Norfolk on 4 July.

Salem was also used to portray the German pocket Battleship Admiral Graf Spee in the 1956 film The Battle of the River Plate, although the original german ship had a single triple gun turret placed forward of the superstructure were the salem has two triple gun turrets forward of its superstructure. The original hull number of the salem, 139, is also clearly visible in many exterior shots of salem

Salem was scheduled for inactivation after her return from the Mediterranean, but the request of Lebanon on 15 August 1958 for aid against an anticipated coup led to a short reprieve for the cruiser. Salem had relieved Northampton (CLC-1) on 11 August as flagship of Commander, 2nd Fleet; and, on 2 September, she departed Norfolk, visited Augusta Bay and Barcelona during a ten-day cruise in the Mediterranean, and returned to Norfolk on 30 September. She reported to the Norfolk Navy Yard on 7 October for inactivation, disembarked the Commander of the 2d Fleet on 25 October, and was decommissioned on 30 January 1959. She was stored as part of the Atlantic Reserve Fleet at the Philadelphia Naval Shipyard.