Mills was born on the Pine Ridge reservation in South Dakota and was orphaned when he was 12. He was then sent to the US Bureau of Indian Affairs boarding school in Lawrence, Kansas. He graduated from the University of Kansas in 1962 and joined the US Marine Corps, where he continued the track and field athletics he had begun in college.
He won the gold medal in the 10,000 meters at the 1964 Olympic Games, the first American to win the event. In 1965 he won and set a new record for the US national 6-mile race championships. After injuries he retired in 1968, and became active in Native American affairs. He was inducted into the National Track and Field Hall of Fame in 1976 and the US Olympic Hall of Fame in 1984.
He now travels promoting physical fitness and as a motivational speaker, is a consultant for the Native American Recreation and Sport Institute, a member of the National Support Committee of the Native American Rights Fund, as well as being a successful insurance executive.
A film was made of his life in 1984, starring Robbie Benson: Running Brave.