City officials had purchased part of the land in the 1830s in anticipation of building a railroad through it, and a workhouse was built there.

In 1846, Mayor Frederick A. Kaye began investigating the possibility of developing a rural or garden-style cemetery on the grounds, a popular concept at the time.

Hartford, Connecticut civil engineer Edmund Francis Lee was hired, who planned a cemetery with winding paths, graves across the tops of hills, and lakes and ponds in the valleys.

Reverend Doctor Edward Porter Humphrey delivered the dedicatory address and elaborated on the idea of the garden cemetery, noting, among other things, that ".

Before the era of large municipal parks, it was common for cities to promote a garden cemetery as a green oasis and recreation destination, and Louisville was no exception.

Several deceased patients from the Brown General Hospital and other nearby army medical facilities were interred in Cave Hill Cemetery.

The entrance lodge and main gates were designed by Louisville architect William H. Reddin in 1880 in the style of Italian Renaissance Revival.

In the 1980s, razor wire was added to the brick walls surrounding Cave Hill to keep out after-hours visitors.

The cemetery currently features more than 500 species of trees and shrubs, including some two dozen current state champion trees, including both native species such as pignut hickory (Carya glabra) and exotics such as Caucasian wingnut (Pterocarya fraxinifolia).

In the addition to Section "O" (lot 267½) are a number of residents of the Kentucky Confederate Home, who died around the start of the 20th century.

[11] Portrait painter and cousin of Mark Twain, Mary Ann Xantippe "Tip" Saunders, was interred at Cave Hill Cemetery in 1922.

Also interred are the founder of Kentucky Fried Chicken, Colonel Harland Sanders; and Mia Zapata, lead singer of punk band The Gits.