 | Fred MacMurray als Cpt. Meriwether Lewis |
 | Charlton Heston als Lt. William Clark |
 | Donna Reed als Sacajawea |
 | Barbara Hale als Julia Hancock |
 | William Demarest als Sgt. Gass |
 | Alan Reed als Charbonneau |
 | Eduardo Noriega als Chief Cameahwait |
 | Larry Pennell als Wild Eagle |
 | Herbert Heyes als President Thomas Jefferson |
 | Lester Matthews als Mr. Hancock |
 | Argentina Brunetti als Shoshone Woman (uncredited) |
 | Julia Montoya als Crow Woman (uncredited) |
 | Ralph Moody als Chief Le Borgne (uncredited) |
 | William Phipps als Night Camp Sentry (uncredited) |
 | Walter Reed als Helmsman Cruzatte (uncredited) |
 | Bill Walker als Tom (uncredited) |
| Helen Wallace als Mrs. Martha Hancock (uncredited) |
| Rudolph Maté | Director |
| Della Gould Emmons | Novel |
| Frank Bracht | Editor |
| Hans J. Salter | Original Music Composer |
| Edmund H. North | Screenplay |
| Winston Miller | Screenplay |
| Daniel L. Fapp | Director of Photography |
| Hal Pereira | Art Direction |
| A. Earl Hedrick | Art Direction |
| William Williams | Second Unit Director of Photography |
| John P. Fulton | Visual Effects |
| Sam Comer | Set Decoration |
| Otto Siegel | Set Decoration |
| Charles C. Coleman | Second Unit Director |
| Wally Westmore | Makeup Supervisor |
| William McGarry | Assistant Director |
| Donald R. O. Hatswell | Technical Advisor |
| Gene Merritt | Sound Recordist |
| Gene Garvin | Sound Recordist |
| William H. Pine | Producer |
| William C. Thomas | Producer |
| Edith Head | Costume Design |
| Bob Herron | Stunts |
