Eggleston was born in Vevay, Indiana. As a child, he was too ill to regularly attend school, so his education was primarily provided by his father. He became an ordained Methodist minister in 1856. His summer home, Owl's Nest, in Lake George, New York, eventually became his year-round home. Eggleston died there in 1902, at the age of 64. Owl's Nest was declared a National Historic Landmark in 1971.