John Barton Payne was born on January 26, 1855, in Prunytown, Virginia (now West Virginia). Prior to becoming a lawyer, Payne was president of the Chicago Law Institute in 1889 and judge of the superior court of Cook County, Illinois, from 1893 until 1898. Earlier in his life, Payne helped the West Virginia Democratic Party and served as mayor of Kingwood, West Virginia. He was also general counsel and later chairman of the U.S. Shipping Board, and he served on the U.S. Railroad administration. Payne practiced law in Chicago firm of Winston, Payne, Strawn & Shaw, from 1902 to 1917.

During the presidential administration of Woodrow Wilson, Payne served as secretary of the interior, from 1920 to 1921, taking over from Franklin Lane. While in power, Payne fervently fought against building reclamation dams in Yellowstone National Park, affirming that the national parks should never be commercialized.

Payne is probably better known as head of the American Red Cross, a position he held from 1921 to until his death in 1935. During that time, he helped establish the Red Cross as a leading organization dedicated to international relief operations. Payne died on January 24, 1935, following complications from an appendectomy.