Middleton graduated from Annadale High School in Annadale, Virginia in 1969. He earned a bachelor's degree in English at Northwestern State University in Natchitoches, Louisiana in 1972; and a master's in history at Louisiana State University in 1973. His thesis traced this history of Fort Jesup west of Natchitoches between 1822 and 1846.
Middleton then moved to New Orleans, Louisiana, where he began writing book reviews for "Figaro", an alternative newspaper. He later contributed columns to The Advocate (Baton Rouge), and Louisiana Life. He came to Birmingham in 1985 to work as an outdoors columnist for Southern Living. His stories also appeared in The New York Times, Field & Stream, Smithsonian magazine, The Progressive Farmer and Southern Accents. Some of his writing appeared under the noms de plume of "Churchill Payne", "Dean McClain", "Paul Sneider", and "Emerson Trout".
Middleton wrote several well-regarded books combining reflections on outdoor pursuits, nature, and his own life. He won awards from the Outdoor Writers Association, the Friends of American Writers, and Southeastern Outdoor Press.
- Middleton, Harry (1989) The Earth is Enough: Growing Up in a World of Trout and Old Men. Simon & Schuster ISBN 9780671674595
- Middleton, Harry (1992) On the Spine of Time: An Angler's Love of the Smokies. Simon & Schuster ISBN 9780671755690
- Middleton, Harry (1992) The Starlight Creek Angling Society. Meadow Run Press
- Middleton, Harry (1993) Rivers of Memory. Pruett Publishing Company
- Middleton, Harry (2000) The Bright Country Pruett Publishing Company
- Kreh, Lefty & Harry Middleton (2005) Lefty's Favorite Fly-Fishing Waters. Lyons Press ISBN 9781592284948
- Middleton, Herry (2016) In That Sweet Country: Uncollected Writings of Harry Middleton. Skyhorse Publishing ISBN 9781634506700
- "Harry F. Middleton Jr" obituary July 30, 1993) The Birmingham News
- Harry Middleton at Findagrave.com