From 1859 to 1862 he was editor of the "Ohio Statesman". He then retired from the newspaper business to become manager of the state public works. In 1876 Manypenny was appointed chair of a special commission to investigate the issues that led to the Sioux outbreak that year, which included the defeat of the American forces under George Armstrong Custer at the battle of the Little Bighorn. In 1880 he wrote "Our Indian Wards" which detailed a variety of wrongs perpetrated on the Indians, along with recommendations for reforms.