- James Stewart as George Bailey
- Donna Reed as Mary Hatch
- Lionel Barrymore as Mr. Potter
- Thomas Mitchell as Uncle Billy
- Henry Travers as Clarence
- Beulah Bondi as Mrs. Bailey
- Frank Faylen as Ernie
- Ward Bond as Bert
- Gloria Grahame as Violet
- H. B. Warner as Mr. Gower
- Frank Albertson as Sam Wainwright
- Todd Karns as Harry Bailey
- Samuel S. Hinds as Pa Bailey
- Mary Treen as Cousin Tilly
- Virginia Patton as Ruth Dakin
- Charles Williams as Cousin Eustace
- Sara Edwards as Mrs. Hatch
- Bill Edmunds as Mr. Martini
- Lillian Randolph as Annie
- Argentina Brunetti as Mrs. Martini
- Bobbie Anderson as Little George
- Ronnie Ralph as Little Sam
- Jeanne Gail as Little Mary
- Jeanine Ann Roose as Little Violet
- Danny Mummert as Little Marty Hatch
- Georgie Nokes as Little Harry Bailey
- Sheldon Leonard as Nick
- Frank Hagney as Potter's Bodyguard
- Ray Walker as Joe (Luggage Shop)
- Charlie Lane as Real Estate Salesman
- Edward Kean as Tom (Bldg. & Loan)
- The Bailey Children
- Carol Coomes as Janie
- Karolyn Grimes as Zuzu
- Larry Simms as Pete
- Jimmy Hawkins as Tommy
Uncredited cast members include:
- Jimmy as Uncle Billy's pet raven
- Stanley Andrews as Mr. Welch, the teacher's husband
- Al Bridge as the sheriff with the arrest warrant against George
- Marian Carr as Jane Wainwright
- Adriana Caselotti as the singer at Martini's
- Ellen Corby as Building & Loan customer Miss Davis
- Dick Elliott as the bald man on his front porch
- Tom Fadden as the bridge tollhouse keeper
- Charles Halton as bank examiner Mr. Carter
- Harry Holman as high school principal Mr. Partridge
- J. Farrell MacDonald as the man whose great-grandfather planted the tree George drives into
- Mark Roberts as Mickey, the student with the swimming pool floor key
- Almira Sessions as Potter's secretary
- Carl Switzer as Freddie Othello, the student who tries to flirt with Mary[12]
- Joseph Granby as the Angel Joseph (voice)
- Moroni Olsen as the Senior Angel Franklin (voice)[13]
