After being commissioned and working up HMS Birmingham joined the 5th Cruiser Squadron on the China Station in January 1938. In September 1939, Birmingham left the China Station for Malta for a refit before joining the Home Fleet in March-April 1940. Birmingham was a unit of the 18th Cruiser Squadron Home Fleet and was involved in patrol work off the coast of Norway for the prevention of German fishing vessels operating in this area. In mid-April HMS Birmingham, HMS Manchester and HMS Cairo were deployed in escorting a troop convoy which left the Clyde and Scapa Flow respectively enroute Harstad, she also landed the 2nd half of the 15th Infantry Brigade at Andalsney and Molde Norway. In May HMS Birmingham in company with the cruiser HMS Manchester they evacuated 1500 troops from Andalsnes. During September-December 1940 she was in refit.

From January until April 1941 HMS Birmingham was tasked in the escorting of troop convoys to the Middle East via the Cape sea route. In May was back up North and when the German battleship Bismarck and the heavy cruiser Prinz Eugen put to sea Birmingham left Scapa Flow to patrol the Iceland-Faroes passage, unfortunately she did not make contact with the German ships. On 4 July 1941 convoy WS-9A arrived in South Africa from the U.K. with the 161 Brigade embarked on passage to the Middle East where it eventually joined the 4th Indian Division, the convoy consisted of 15 ships, Birmingham arrived with this convoy, and later that month she docked in the Selborne dry dock at Simonstown, where she was fitted with the Mk284 and 291 radars and several new AA weapons.

After completion of this refit in February 1942, HMS Birmingham was transferred to the Eastern Fleet. In March she was once agian docked in the Selborne dry dock. In June she was a member of the 4th Cruiser Squadron operating in the Mediterranean under Rear Admiral Tennant, she made up part of the covering force for the double convoy operation code named operation "Harpoon" and "Vigorous" from Gibraltar and Alexander to supply the island of Malta. Later that month, she was attacked and damaged by 15 JU 87 and Italian Cant 1007 aircraft. They damaged the cruiser with near misses. In September she was back in the Indian Ocean and was involved in operation "Stream" the British operation to occupy Madagascar. In November Birmingham was involved in transporting a convoy to Majunga West Coast where the 10th Infantry Brigade was landed. Air escort was provided by the carrier HMS Illustrious.

In April 1943 Birmingham returned to U.K. for a refit. In October, her refit completed, she once more returned to the Mediterranean theatre where on 28 November HMS Birmingham was torpedoed by the German submarine U-407 off the coast of Cyrenaica in position 33.05N, 21.43E, she was very seriously damaged, however she succeeded in returning to Alexandria where temporary repairs were carried out on her. In June 1944, Birmingham sailed from Alexandria bound for the U.S.A. where permanent repairs were carried out. In November 1944, the repairs were completed and she returned to home waters to join the 10th Cruiser Squadron at Scapa Flow.

In May 1945 a British force under Captain Williams was tasked to occupy ports in the northern area, the force consisted of HMS Birmingham, HMS Dido and several destroyers, they passed through the German mine barrage off the Skaggerack and reached Copenhagen on May 9th, where the German cruisers Prinz Eugen and Nurnberg lay after their surrender. On the 13th of that month Birmingham was relieved of her duties by the cruiser HMS Devonshire. After the war in 1948 Birmingham was transferred to the South Atlantic Command. During 1949-1950 Birmingham served in the East Indies Fleet with the 4th Cruiser Squadron. During 1950-1952 Birmingham underwent a modernisation, receiving new bridgework a lattice foremast and air conditioning enabling her suitable for service in the Far East. To control the 4" A/A armament, she was given 2 - Mk 6 high angle directors at the corners of the former aircraft hanger. After this modernisation no more work was carried out on her as she was considered too be too old to justify any major modernisation. After this refit she was transferred to the Far East Fleet, where she was a member of the 5th Cruiser Squadron. In June 1952 as the Panmunjom (Korea) negotiations moved belatedly towards an armistice Birmingham in company with HMS Newcastle and two frigates supported American landing craft evacuating thousands of friendly Koreans from islands off the north-west coast. In June 1954, Birmingham returned home from the Far East. Whilst involved in the Korean conflict, she had expended 1,051 six inch shells. In 1955 Birmingham was transferred to the Mediterranean Fleet, where she joined the 1st Cruiser Squadron as flagship. In June 1957, C. in C. Mediterranean, Admiral Sir Ralph Edwards in Birmingham with seven other warships, exercised off the Turkish Black Sea ports, this led to a strong protest from the Russian government. In May 1959 while still operating from Malta, Birmingham was involved in a collision with the destroyer Delight which caused the deaths of two sailors who were overcome by fumes while inspecting areas below the cruisers waterline for damage. On 3 December 1959 the cruiser was paid off at Devonport, being the last of the class in service. In September 1960 Birmingham was broken up for scrap by Ward of Inverkeithing. Her badge can be seen displayed on the Selborne dry dock wall at Simonstown, South Africa.

Commanding Officers:
Capt. Eric James Patrick Brind, RN
3 January 1938 - 4 March 1940

Capt. Alexander Cumming Gordon Madden, RN
4 March 1940 - 15 December 1941

Capt. Henry Berwick Crane, RN
15 December 1941 – 6 September 1943

Capt. Herbert Wyndham Williams, RN
6 September 1943 – still in command in October 1945 according to the Navy List

Hit by U-boat
Damaged on 28 Nov 1943 by U-407 (Brüller).