Gist was one of the first European-Americans to explore what is now West Virginia. Born near Baltimore, he worked as a trader, surveyor, and road builder. After losing his business in a fire, he moved to North Carolina around 1745.

In 1750, Gist was hired to explore land west of the Allegheny Mountains. He traveled through parts of West Virginia, Ohio, and Kentucky. In 1753, he helped guide young George Washington on a mission to Fort Necessity to warn the French to leave British-claimed land. During the French and Indian War, Gist worked as a guide for General Braddock’s failed attack on Fort Duquesne. In 1755, he joined the Virginia army, led by George Washington, and served as captain of scouts.