Kephart was born in Pennsylvania and raised in Iowa. He was the director of the St. Louis Mercantile Library in St. Louis, Missouri from 1890 to 1903. In these years Kephart also wrote about camping and hunting trips. Earlier, Kephart had also worked as a librarian at Yale University and spent significant time in Italy as an employee of a wealthy American book collector.
In 1904, Kephart's family (wife Laura and their six children) moved to Ithaca, New York, but Laura and Horace never divorced or legally separated. Horace Kephart found his way to western North Carolina, where he lived in the Hazel Creek section of what would later become the Great Smoky Mountains National Park:
- "I took a topographic map and picked out on it, by means of the contour lines and the blank space showing no settlement, what seemed to be the wildest part of these regions; and there I went."
Later in life Kephart campaigned for the establishment of a national park in the Great Smoky Mountains with photographer and friend George Masa, and lived long enough to know that the park would be created. He was later named one of the fathers of the national park. He also helped plot the route of the Appalachian Trail through the Smokies. Kephart died in a car accident in 1931, and was buried near Bryson City, North Carolina, a small town near the area he wrote about in Our Southern Highlanders. Two months before his death, Mount Kephart was named in his honor.