After a series of supporting film and television roles in the late 1990s, she landed her breakthrough role as Bridget Hennessy on the ABC sitcom 8 Simple Rules, on which she starred from 2002 to 2005. After that, Cuoco appeared as Billie Jenkins in the final season of the television series Charmed (2005–2006).
She has also starred as Penny on the CBS sitcom The Big Bang Theory (2007–2019), for which she has received Satellite, Critics' Choice, and People's Choice Awards. Cuoco's acting work includes roles in To Be Fat like Me (2007), Hop (2011), The Flight Attendant, and Authors Anonymous (2014). She received a star on the Hollywood Walk of Fame in 2014. In October 2017, Cuoco founded Yes, Norman Productions.