She spent most of her career operating in the Mediterranean from mid 1941 under the command of Captain Arthur Hezlet, where she sank the Italian passenger/cargo ship Fenicia and the Italian troop transport Esperia. She also damaged the Italian cargo ship Arsia, which was later declared a total loss. On 5 January 1942, she made an unsuccessful attack on the .[1]
Unique left Holy Loch after a refit, for a patrol in the Bay of Biscay on 7 October 1942. She left her escort off the Scillies on 9 October. No more was seen or heard from her after that date. was in the area on 10 October and reported hearing underwater explosions that led her to believe Unique was under attack, although the Germans made no claims of her sinking. She was reported overdue on 24 October 1942 when she failed to arrive at Gibraltar.[2]