Otto Henning qualified (Dr Med Vet) at the University of Stuttgart, Germany, in 1885, after which he was appointed assistant in the Pathological and Bacteriological Institute of the Veterinary High School at Stuttgart. Two years later he became district veterinary surgeon for the district of Creilsheim. Early in 1892 he emigrated to Cape Town, where he was appointed in April as assistant veterinary surgeon in the Cape of Good Hope administration. The next year he became the first to prove the toxicity of Cynanchus ellipticum (Monkey rope) when he caused poisoning in sheep that had been experimentally fed on the plant. During the summer of 1893-1894 he investigated "Lewersiekte" (parathyroid disease) among calves. His report on this work was published by the Department of Agriculture, as well as in the Agricultural Journal of the Cape of Good Hope in 1894.
In 1896 Henning was seconded to the Orange Free State to assist with the control of rinderpest and from 1897 to 1900 was state veterinary surgeon of that territory and a member of its Agricultural Council. After the occupation of Bloemfontein by the British in 1900 he filled various short-term positions: Divisional veterinary officer to the South African Constabulary (1900-1901), government veterinary surgeon of Basutoland (now Lesotho, 1901-1902), principal veterinary officer to the Repatriation and Government Relief Department in the Orange River Colony (1902-1904), and chief veterinary surgeon of Basutoland (1904-1907). In 1906 the government of Basutoland sent him to Natal to gain experience of east coast fever.
In December 1907 Henning was appointed chief of agriculture in German South West Africa (now Namibia) where he served until that territory was captured by the South African forces in 1915, during World War I (1914-1918). In 1921 he was reinstated and served as government veterinary officer at Keetmanshoop until 1923, when he retired to take up farming in the Grootfontein district.