A crockery store clerk when the American Civil War broke out, Miles joined the army as a volunteer and fought in several battles. He rose to the rank of major general.

He later played an important part in the U.S. army's campaigns against the native Americans of the Great Plains. He was a field commander in the 1874-75 Red River campaign against the Kiowa, Comanche and Southern Cheyenne. He led the 1876-77 campaign against the Northern Plains First Nations who had just defeated Custer at the Little Bighorn and intercepted Chief Joseph and his Nez Perce before they could reach the border and join Sitting Bull in Canada.

It was under Miles's general orders that Custer's reorganized 7th Cavalry killed many followers of Chief Si Tanka (Big Foot) in what became known as the Wounded Knee Massacre of 1890.