At 1:25 on 22 June Ascianghi sighted a large armed merchant, of about 15,000 tons, and attacked her with four torpedoes, but they all missed due to stormy weather and rough seas.

Towards the end of January 1941, as British Forces left Gibraltar to bombard Genoa, Ascianghi was deployed as a defensive screen about twenty miles southwest of Cape Mele, however, due to bad weather, the British Naval forces returned to the port and aborted their mission.

The next day at 21:46 she intercepted an old steamer Antar (389 GRT, 1890), sailing under Palestinian flag, but employed by the British, in the position 33°57′N 35°04′E / 33.950°N 35.067°E / 33.950; 35.067, 8 nautical miles northwest of Beirut, during a Port Said-Mersin trip with a cargo of cotton, tea and tinplate.

Towards mid-June 1942, along with four other submarines, including Aradam and Dessiè she patrolled between Malta, Pantelleria and Lampedusa with the task of engaging British convoy "Harpoon".

Also, on 3 November 1942, she carried about twenty German soldiers who survived an air crash and picked them up in the Mediterranean and brought them to Libya.

On 15 November, in the Bay of Bougie, she sighted a small group of British ships leaving the harbor, mistakenly identifying them as a cruiser escorted by two destroyers.

On the night of 2 March 1943, while on mission in the Gulf of Sirte, Ascianghi sighted a convoy with several escorts and launched three torpedoes against a destroyer from 800 meters.

After that Ascianghi remained at the base for repairs and maintenance work, captain Erler was replaced by a young officer Mario Fiorini.

On 16 July 1943 the submarine left Naples heading to an area southeast of Sicily, to attack the supply lines for Allied troops that landed on the island.

In the afternoon of 23 July 1943 while patrolling submerged ten miles from Augusta Ascianghi detected a group of enemy cruisers and destroyers.

Ascianghi plummeted below the test depth, and to avoid being destroyed by pressure, she was forced to surface and try fighting it out with her deck gun.