The second U-81 was a Type VIIC submarine of the Kriegsmarine. Her keel was laid down May 11, 1940, by [Bremer Vulkan]?, of Bremen-Vegesack?. She was commissioned April 26, 1941 with Oberleutnant zur See Friedrich Guggenberger in command. Guggenberger remained in command, receiving a promotion to Kapitänleutnant, until December 1942 when he was relieved by Oblt. Johann-Otto Krieg, who commanded her until the end of her career.
U-81 conducted 17 patrols, sinking 23 ships totalling of 63,289 tons and damaging two others totalling 14,143 tons. On November 13, 1941, she sank the British aircraft carrier HMS Ark Royal in the Mediterranean.
On January 9, 1944, at 11:30am, U-81 was sunk at Pola by US bombs and two crewmen were killed. She was raised on April 22, 1944, and broken up.