- Jean Arthur as Saunders
- James Stewart as Jefferson Smith
- Claude Rains as Senator Joseph Paine
- Edward Arnold as Jim Taylor
- Guy Kibbee as Governor Hopper
- Thomas Mitchell as Diz Moore
- Eugene Pallette as Chick McGann
- Beulah Bondi as Ma Smith
- H. B. Warner as Senate Majority Leader
- Harry Carey as President of the Senate
- Astrid Allwyn as Susan Paine
- Ruth Donnelly as Mrs. Hopper
- Grant Mitchell as Senator MacPherson
- Porter Hall as Senator Monroe
- Pierre Watkin as Senate Minority Leader
- Charles Lane as Nosey
- William Demarest as Bill Griffith
- Dick Elliott as Carl Cook
- The Hopper Boys:
- Billy Watson
- Delmar Watson
- John Russell
- Harry Watson
- Gary Watson
- Baby Dumpling
- H. V. Kaltenborn as himself
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Uncredited
- Russell Simpson as Kenneth Allen
- Dick Jones as Richard "Dickie" Jones, Senate Page Boy
- Anne Cornwall as Senate Reporter
- Gino Corrado as Barber
- Maurice Costello as Diggs – Newsman
- Alec Craig as Speaker
- Lew Davis as Senate Clerk
- Vernon Dent as Senate Reporter
- Harry Depp as Hat Salesman / Secretary
- Robert Middlemass as 2nd Radio Announcer
- Gladys Gale as Committee Woman
- Stanley Andrews as Senator Hodges
- Harlan Briggs as Mr. Edwards, howling citizen
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Cast notes:
- Among the unbilled veteran character actors seen in the film are Guy Kibbee's brother, Milton Kibbee, who has a bit as a reporter; Lafe McKee; and Matt McHugh of the McHugh acting family. Also in the film in minor roles are Dub Taylor and Jack Carson, later well-known actors. Silent film character player Hank Mann played a photographer.
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