The ship was launched on 20 August 1927. The christening took place in the presence of Dr. Finter, the mayor of Karlsruhe, and the widow of Erich Köhler, the commander of the previous SMS Karlsruhe, who was lost in the sinking of the ship on 4 November 1914. During the transfer from Kiel to Wilhelmshaven (through the Kiel Canal on 15 October 1929), the sea trials were validated. The Karlsruhe was commissioned on 6 November 1929 in Wilhelmshaven under the command of Eugen Lindau. From May 1930 to June 1936, the cruiser was used as a training ship for officers during five long training cruises across the world’s oceans. On the fifth cruise in 1935 and 1936, during a crossing between Japan and the United States, the ship suffered heavy damage due to a storm and had to be laid up in San Diego for repairs. From 1 July 1936, the ship was used for scouting missions. During the Spanish War, the Karlsruhe patrolled Spanish and Portuguese waters in January-February and June 1937. In order to improve her seaworthiness in stormy weather, the ship returned to the Kriegsmarinewerft in Wilhelmshaven on 20 May 1938. When the war started, the work was not finished. She remained in dry dock until 13 November 1939 for further trials.
With a new, insufficiently trained crew, the Karlsruhe took part in Operation Weserübung in April 1940. Under the command of Kapitän zur See Friedrich Rieve, the cruiser’s task was to support the landing of German troops at Kristiansand. The German forces captured the port city in the third attempt, after first fighting two artillery duels with the Norwegian coastal artillery. During the retreat into the Skagerrak, on 9 April at 19:58, the British submarine HMS Truant torpedoed it. Both engines, the electrical system and the rudder were out of action. The Karlsruhe listed rapidly and then began to sink. At 21:00, the crew was picked up by the torpedo boats Luchs and Seeadler. Captain Rieve then ordered the torpedo boat Greif to finish off the wreck. The order was executed at 10.50 pm, two torpedoes were launched and the Karlsruhe was finally sunk. Wreck, located in April 2017, was formally identified in the Norwegian trench, 11 nautical miles south-east of Kristiansand in June 2020 at a depth of 490 metres, about 15 metres from the underwater power cable Cross-Skagerrak.