Humans have lived in the area around Natural Bridges since as early as 7500 BCE, as shown by rock art and stone tools found at nearby sites.

Around 700 CE ancestors of modern Puebloan people moved to the site, constructing stone and mortar buildings and granaries.

The park received little visitation until after the uranium boom of the 1950s, which resulted in the creation of new roads in the area, including modern-day Utah State Route 95, which was paved in 1976.

The Sipapu, Kachina, and Owachoma bridges were formed through rock decay, weathering and erosion, as water cut through narrow canyon walls.

The Monument's pygmy rattlesnakes have been the subject of occasional study; several lizard species common to southern Utah are abundant.

In May 2006, KSL Newsradio reported a case of plague found in dead field mice and chipmunks at Natural Bridges.

[10] Native plant species include willow, cottonwood, Douglas fir, ponderosa pine, pinyon pine, juniper, grasses, annuals, and perennials such as asters, penstemons, buckwheats, and Indian paintbrush, and various shrubs such as dwarf oaks, bayberry, manzanita, buffaloberry, rabbitbrush, black brush, brittle brush, Apache's plume, sage, yucca, and Mormon tea.