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 demonstrated a strong interest in acting and was cast in school plays. After graduating, she made her onscreen debut in the TV movie From Where I Sit in 2000. This marked the beginning of her journey in the entertainment industry.
Caplan's early career was marked by appearances in various TV shows, including Freaks and Geeks in 1999, Smallville in 2001, and The Pitts in 2003. She made her big screen debut with a small role in Orange County in 2002, followed by a memorable performance as Janis Ian in the hit film Mean Girls in 2004.
Throughout the 2000s, Caplan continued to build her reputation as a talented actress. She appeared in Cloverfield in 2008, Hot Tub Time Machine in 2010, and 127 Hours in 2010. These roles showcased her versatility and range as a performer.
In the 2010s, Caplan took on the role of Virginia Johnson in the television series Masters of Sex in 2013, earning an Emmy nomination for her performance. She also co-starred in The Interview in 2014, opposite Joseph Gordon-Levitt, and appeared in The Night Before in 2015, alongside Seth Rogen and Anthony Mackie.
More recently, Caplan has appeared alongside a talented ensemble cast in Now You See Me 2 in 2016, starring Jesse Eisenberg, Dave Franco, Woody Harrelson, and Daniel Radcliffe. Throughout her career, Caplan has consistently demonstrated her ability to adapt to a wide range of roles and genres, cementing her status as a talented and versatile actress.