Josiah Gregg was born on 19th July 1806 in Overton Country (Tennessee). When he was six years old his family moved to Missouri.Gregg had training in both law and medicine, and practiced both with distinction before he retired from urban life due to deteriorating tuberculosis.

In 1831 he joined a caravan for Santa Fe, on a new trail from Van Buren (Arkansas) to Santa Fe. Gregg then he settled in New Mexico Territory, starting work as a bookkeeper. He made a tour of Indian Territories - Oklahoma Territory.

Josiah Gregg's book, "Commerce of the Prairies," which came out in two volumes in 1844 was an account of his time spent as a trader on the Santa Fe Trail from 1831 to 1840 before the Mexican-American War. This included extensive descriptions of the geography, botany, geology, and culture of New Mexico. Gregg wrote of some locals, such as Maria Gertrudis Barceló, a Santa-Fe saloon owner.

The book established Gregg's literary reputation, and he was hired as a news correspondent and interpreter during the Mexican-American War. In this capacity, he traveled through Chihuahua.

Gregg corresponded with George Engelmann in St. Louis, Missouri, sending him collections of plants, many of which were previously undescribed. Several Southwestern plants bear the species patronym "greggii" to honor Gregg's contributions.

After the war, in 1849 Gregg participated in the California Gold Rush. He died from starvation and exposure, 25th February 1850, while leading an emergency winter expedition out of a snow bound mining camp. The expedition has been credited with the rediscovery of Humboldt Bay, that resulted in its settlement.