- Andy Griffith as Sheriff Andy Taylor: The widowed father of Opie and town sheriff of Mayberry.
- Ron Howard as Opie Taylor: Andy's son and a student at Mayberry Elementary School.
- Don Knotts as Deputy Barney Fife: Andy's accident-prone deputy.
- Frances Bavier as Aunt Bee Taylor: Andy's widowed aunt and Opie's grandmother.
- Jim Nabors as Gomer Pyle: A dim-witted gas station attendant and friend of Andy and Barney.
Recurring Characters:
- Howard McNear as Floyd Lawson: The town barber.
- Rance Howard as Mr. Howard: The town pharmacist.
- Jack Dodson as Howard Sprague: The town clerk and town gossip.
- Hal Smith as Otis Campbell: The town drunk.
- Thelma Lou as Thelma Lou Sackett: Barney's girlfriend.
- Mayberry Trio: A local band consisting of Goober Pyle (played by George Lindsey), Ernest T. Bass (played by Howard Morris), and Johnny Paul Jason (played by Johnny Paul Jason).