30 Oct 1941
The boat was attacked by a British Catalina flying boat (RAF Sqdn 209/Z, pilot Denis E. Ryan) SW of Brest while enroute to cross the Straits of Gibraltar. A Hudson bomber (Sqdn 53, F/O Henry) also appeared and dropped depth charge. The boat was severely damaged and had to return to Brest. After hurried repairs the boat once more sailed for the Mediterranean. (Sources: Blair, vol 1, page 396)

13 Nov 1941
U-81, having recently entered the Mediterranean, learned the British Force H was passing through on its way to Gibraltar. She managed to intercept, and fired from extreme range to sink the aircraft carrier HMS Ark Royal. The destroyer escort delivered a punishing depth charge attack with 130 depth charges counted, but the boat escaped. (Sources: Blair, vol 1, page 396)

27 Jun 1943
U-81 had to retreat when shelled by coastal artillery after sinking Michalios three miles west of Latakia, Syria.

9 Jan 1944
The sinking of U-81: At 11.30 hrs on 9 January 1944, as U-81 was making final preparations to sail at 16.00 hrs on its 18th war patrol, the harbour of Pola was hit by 319 tons (290 tonnes) of bombs dropped by 107 B-17 Flying Fortresses of the 2nd, 97th, 99th and 301st BG, 15th AAF. One bomb hit the U-boat near the aft torpedo hatch and passed completely through the pressure hull, killing two men on watch. Flooding of the stern compartments caused U-81 to settle so fast that the crew had no time to close the bulkhead to the control room, and the U-boat sank, capsized to port in shallow water.

4 recorded attacks on this boat.