Born to poor parents, he attended newly founded Deerfield Academy, where he was later principal, from 1815 to 1818.

His chief project, however, was natural theology, which attempted to unify and reconcile science and religion, focusing on geology.

In this book, he sought out ways to re-interpret the Bible to agree with the latest geological theories.

For example, knowing that the earth was at least hundreds of thousands of years old, vastly older than the 6,000 years allowed by certain biblical interpretations, Hitchcock devised a way to read the original Hebrew so that a single letter in Genesis—a "v", meaning "afterwards"—implied the vast timespans during which the earth was formed.

Randy Moore described Hitchcock as "America's leading advocate of catastrophism-based gap creationism.

[2] He published papers on fossilized tracks in the Connecticut Valley, including Eubrontes and Otozoum, that were later associated with dinosaurs, though he believed, with a certain prescience, that they were made by gigantic ancient birds.

His son, Edward "Doc" Hitchcock Jr., named one of the earliest dinosaurs discovered in North America and the United States, Megadactylus polyzelus.

[8] His collections, a bust and portrait can be viewed at the Amherst College Museum of Natural History.

After his death in 1864, his son Charles Henry Hitchcock (1836–1919) published a new edition (1870) also without a paleontological chart.