Weddigen was born in Herford, in the Prussian Province of Westphalia and started his military career in the Kaiserliche Marine in 1901. In 1910 he was given command of one of the first German submarines, U-9.

In the action of 22 September 1914, while patrolling in the region of the southern North Sea known to the British as the "Broad Fourteens", U-9 intercepted the three warships of the Seventh Cruiser Squadron. Weddigen fired off all six of his torpedoes, reloaded while submerged, and in less than an hour sank the three British armoured cruisers HMS Aboukir, HMS Hogue and HMS Cressy. Sixty two officers and 1,397 other men were killed, leaving 837 survivors. Weddigen was awarded the Iron Cross, second and first class for this action.

After sinking HMS Hawke and some merchant ships, Weddigen received Prussia's highest military order, the Pour le Mérite. He also received the highest military honours of the other kingdoms of the German Empire: The Knight's Cross of the Military Order of Max Joseph of the Bavaria (making him one of only six non-Bavarians to receive this), the Knight's Cross of Saxony's Military Order of St. Henry and the Knight's Cross of Württemberg's Military Merit Order.

Weddigen died while commanding the submarine U-29. On 18 March 1915 U-29 was submerged in the Pentland Firth. U-29 fired a torpedo at HMS Neptune and subsequently broke the surface immediately ahead of the British battleship HMS Dreadnought. After a short chase U-29 was rammed by Dreadnought which cut the submarine in two. There were no survivors from the submarine.

During the inter-war period, the resurgent Wehrmacht named a newly built barracks in Herford as Otto-Weddigen-Kaserne (renamed Harewood Barracks) in his honour due to the linkage with Weddigen's birthplace. Although the Wehrmacht unit housed inside the barracks was Panzer Abwehr Abteilung 6, an Army anti-tank unit, the occupants nevertheless signified the naval connection to Weddigen by placing two large anchors at the base of a large National Socialist Reichsadler at the entrance to the barracks. Ironically, ever since 1945 the barracks has been occupied by British Army soldiers from the Royal Armoured Corps, various other tank units and finally the Royal Corps of Signals. The barracks was scheduled to close with the withdrawal of British Forces in Germany in 2020.

• Edwards, Bernard (1996). Dönitz and the Wolf Packs – The U-Boats at War. London, UK: Cassell Military Classics. pp. 11–12. ISBN 0-304-35203-9.

• Newspaper clippings about Otto Weddigen in the 20th Century Press Archives of the ZBW