After the boat was commissioned, she underwent trials at Taranto and then sailed to her assigned base at the Red Sea port of Massawa.

[3] After Italy entrance into World War II in June 1940, Archimede was ordered out to sea to patrol off the coast of French Somaliland.

On 20 June some members of the crew fell sick due to leaking chloromethane from the air conditioning system, however no one paid attention to that at the time.

During the night of 23 June four sailors died due to chloromethane poisoning, and at that point Commander Signorini decided to stop the mission and return to base.

Twenty four seriously poisoned men, including Commander Signorini and the chief machinist, were disembarked, and two of them later died bringing the total number of casualties to six.

Archimede then was kept in port until September 1940 undergoing repairs, and the refrigerant in her air conditioning system was changed from chloromethane to freon.

[4] During her second war mission, she was deployed off Perim Island for seven days, leaving Massawa on 20 December 1940 but she sighted no enemy traffic.

[3] In January 1941, when it became clear that Italian East Africa would eventually fall, it was decided to send submarines to Bordeaux to try to save them from either destruction or capture by the British.

All submarines were modified for the journey: their fuel tanks were enlarged, some torpedoes, gun ammunition were removed as well as some non-critical items.

[5] Archimede, under command of captain Mario Salvatori, left on 3 March 1941 together with Guglielmotti and headed to Bordeaux, in the occupied part of France.

Overall, Archimede traveled more than 12,700 nautical miles (23,500 km; 14,600 mi) in 65 days to conclude her seventh war patrol.

She continued to operate about 600 miles west of Gibraltar and returned without any further incident to Bordeaux on 17 November to undergo two months worth of repairs.

Archimede launched two torpedoes, and explosions were heard, but the submarine had to dive and undergo a depth-charge attack by the destroyers.

Finally on 15 June, on the Buenos Aires – Trinidad route she sighted a cargo ship SS Cardina (5,586 GRT) running under a Panamanian flag and carrying 7,000 tons of Linseed.

[7] On 15 September 1942 Archimede under command of captain Guido Saccardo departed for another patrol mission in the area between Freetown and Cape São Roque.

[8] After cruising in her zone for a few days, she sighted a British ocean liner converted to troopship SS Oronsay (20,043 GRT) early in the morning of 9 October 1942.

[9] During the following night Archimede attacked another ocean liner converted to troop transport, SS Nea Hellas (16,991 GRT).

Finally, at 15:10 on 15 April 1943 United States Navy Consolidated PBY Catalina PBY-5A (83-P-5) of Squadron VP-83 based on Natal, Brazil while flying at 7,300 ft, sighted the submarine traveling surfaced at about 5–7 knots.

[10] The submarine sustained damage to her forward hatches which were blown off, the lighting installations were smashed and one diesel engine was rendered inoperative.

On the twenty ninth day after the sinking the raft washed ashore on the Island of Bailique near the Western shore of the Amazon River; there was only one survivor found alive weak and delirious by two Brazilian fishermen.