Actress Elizabeth Anne "Lizzy" Caplan was born in Los Angeles, California, to Barbara (Bragman), a political aide, and Richard Caplan, a lawyer. She has two older siblings, Julie and Benjamin, and was raised in a Jewish household. Her mother was a cousin of publicist Howard Bragman. Caplan was educated at Alexander Hamilton High School, where she showed an interest in acting and was cast in school plays.

Caplan made her onscreen debut in the TV movie "From Where I Sit", followed by "Freaks and Geeks", "Smallville", "Related", "The Class", "New Girl" and "Party Down". She made her big screen debut with a small role in "Orange County" and went on to gain wider recognition with roles in the films "Mean Girls", "Cloverfield", "Hot Tub Time Machine", "127 Hours", "The Interview" and "Now You See Me 2". In 2013, Caplan portrayed Virginia Johnson in the television series "Masters of Sex", for which she received a Primetime Emmy, Satellite, and Critics' Choice Award nominations for Outstanding Lead Actress.

In 2019, Caplan announced that she'd be appearing as the main lead as Annie Wilkes on "Castle Rock".

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