[1] For surface running, the boats were powered by two 600-brake-horsepower (447 kW) diesel engines, each driving one propeller shaft.

At the outbreak of hostilities she immediately was sent on a mission to the west part of the Gulf of Genoa and returned on 14 June 1940 without encountering any enemy traffic.

On 1 August 1940 Neghelli together with Scirè, Argo, Turchese, Medusa (later replaced by Luciano Manara), Axum and Diaspro was sent to form a barrier north of Cape Bougaroun following departure from Gibraltar of the British Force H. There were ongoing British operations "Crush" and "Hurry" in progress at this time.

Two more submarines, Naiade and Narvalo, were also deployed in the same area to intercept British naval forces sent to attack Italian ports on the coast of Cyrenaica.

On 13 December 1940, at 20:22 while patrolling on the surface in an area 45 miles north of Marsa Matruh in the position 32°37′N 26°44′E / 32.617°N 26.733°E / 32.617; 26.733, she sighted a British cruiser thought to be HMS Southampton.

One of Neghelli 's torpedoes struck the steamer Clan Cumming (7264 GRT) in the position 37°15′N 24°04′E / 37.250°N 24.067°E / 37.250; 24.067, near the San Giorgio island, causing serious damage and forcing her to return to Piraeus escorted by HMS Janus.

The remaining destroyers counterattacked with depth charges, and finally HMS Greyhound was able to hit the submarine, which sank with all hands 40 miles northeast of Falkonera.