In the afternoon of November 9, 1940 Axum left Cagliari and was sent to patrol off the island of La Galite along with four other submarines (including Alagi and Aradam) as a screen to the British Operation "Coat".

The ship returned fire and the submarine was forced to dive and get through a brief but intense depth charge attack, without suffering any damage.

On January 4, 1942 Axum was deployed to an area south of Malta with the task of detecting and attacking any British naval forces, but no sightings were made.

Altogether, fifteen Italian submarines and two German U-Boots were deployed in the western Mediterranean with the orders to attack any enemy ship greater than a destroyer.

On August 11, 1942, the submarine, commanded by captain Renato Ferrini, left Cagliari heading to an area 25 miles northwest of Cape Blanc, where he arrived the following day.

At 6:00 on August 12, Axum left his assigned area, and at 14:00 Commander Ferrini, believing that the convoy would be going a lot closer to the coast, keeping their escorts to the north, ordered full ahead towards Cape Blanc while under water.

[3] The first torpedo struck modern light cruiser HMS Nigeria, flagship of Admiral Harold Burrough (Commander of Force X), moving at 14 knots.

The ship started listing to port (i.e. to the left), but the crew managed to stabilize the cruiser and was able to turn around and head to Gibraltar accompanied by three destroyers.

HMS Nigeria safely made it back to Gibraltar, where she stayed for over a year undergoing repairs returning to action in September 1943.

The ship was hit by several bombs on her journey, but the superhuman determination of her crew, and support of several destroyers that guarded her, allowed SS Ohio to reach Malta on 15 August 1942.

The damage sustained by the submarine prevented her from diving below 40 meters; nevertheless, Axum stayed in the area patrolling for the next 2 days, and returned to Trapani on August 15, 1942, at 19:30.

On November 7, 1942, she sighted enemy ships, but got detected and had to dive and withstand a barrage of depth charges which caused some damage.

On April 11, 1943, while sailing in a violent storm off the coast of Sardinia, sustained flooding and lost the use of both of her periscopes forcing her to abandon her mission and return to the base.

At the announcement of the armistice, on September 8, 1943 Axum (under command of captain Vittorio Barra) was in Gaeta to carry out repair work on diesel engines.

[3] For the rest of the war, Axum was used only to infiltration missions (bringing and taking spies and sabotage teams from German-occupied territories).

During one of those missions, on December 25, 1943 Axum, under command of captain Giovanni Sorrentino, left Taranto to recover spies from the Gulf of Kyparissia.

While waiting for a sailboat to bring back the spies, Axum was drifting towards the coast when she ran aground on unknown rock formation.

[5][3] All efforts to dislodge the submarine failed, so in the afternoon of December 28, 1943 commander Sorrentino ordered the boat scuttled with explosive charges at Kaiafas beach, in the position 37°31′N 21°35′E / 37.517°N 21.583°E / 37.517; 21.583.

Finally, at the end of January 1944, the crew and the spies were picked off Marathopolis (now part of Gargalianoi), near Proti Island by escort Ardimentoso.