- Iain Armitage Sheldon Cooper
- Zoe Perry Mary Cooper
- Lance Barber George Cooper, Sr.
- Annie Potts "Meemaw"
- Montana Jordan George Cooper, Jr.
- Raegan Revord Missy Cooper
The casting of Iain Armitage as Sheldon and Zoe Perry as Mary Cooper was announced in early March 2017. When CBS ordered Young Sheldon to series later that month, CBS revealed that Lance Barber would play Sheldon's father, George Sr., while Montana Jordan would star as his older brother, George Jr., and Raegan Revord would play Missy, Sheldon's twin sister.
In July 2017, Annie Potts joined the cast of Young Sheldon as Sheldon's Meemaw, who was described as a foul-mouthed, hard-drinking Texan grandmother who is very supportive of her grandson's talents.