Fred MacMurray as Cpt. Meriwether Lewis

Charlton Heston as Lt. William Clark

Donna Reed as Sacajawea

Barbara Hale as Julia Hancock

William Demarest as Sgt. Gass

Alan Reed as Charbonneau

Eduardo Noriega as Chief Cameahwait

Larry Pennell as Wild Eagle

Herbert Heyes as President Thomas Jefferson

Lester Matthews as Mr. Hancock

Argentina Brunetti as Shoshone Woman (uncredited)

Julia Montoya as Crow Woman (uncredited)

Ralph Moody as Chief Le Borgne (uncredited)

William Phipps as Night Camp Sentry (uncredited)

Walter Reed as Helmsman Cruzatte (uncredited)

Bill Walker as Tom (uncredited)

Helen Wallace as Mrs. Martha Hancock (uncredited)