[1] She is the youngest of five children of Marjorie (née Coll), a high school teacher and gourmet home chef, and Michael Prepon, an orthopedic surgeon.

[2] She attended Watchung Hills Regional High School until she was 15, then studied at the Total Theatre Lab in New York City.

[6] Later, in September 1997, she premiered on a Levi Strauss-developed show called They Go On, an Internet-based soap opera.

[10] In 2001, she made her film debut in Steve Hanft's musical comedy-drama Southlander with Beck, Beth Orton and Hank Williams III, where she played Seven=Five, a young TV telepathic.

[11] Prepon had a cameo voice appearance as a United Nations Space Command marine in Halo 2, which was released in 2004.

[12] Her first notable film role came in 2004 with the dark drama Lightning Bug with Bret Harrison, Kevin Gage and Ashley Laurence.

[13] In 2006, Prepon co-starred with Misha Collins in the psychological thriller Karla, based on the true story of Paul Bernardo and his wife Karla Homolka, a Canadian couple who kidnapped, sexually abused, and murdered three girls, marking a contrast to her usual lighthearted roles.

[15] Prepon co-starred with Bryan Greenberg as Hannah Daniels in the ABC drama October Road, which debuted March 15, 2007.

[16] On February 5, 2010, it was announced that Prepon signed on to star in Awkward Situations for Men, a pilot on ABC.

[17] In 2009, Prepon appeared in the CBS sitcom How I Met Your Mother as Karen, one of the girlfriends of Ted Mosby (Josh Radnor), in the episode "Sorry, Bro".

She directed a short film, Abide with Me, about a 10-year-old boy who, "upon bearing witness to his father's murder, is rendered mute".

[20] Prepon had been working on a web series, Neighbros, which she directed and edited, starring her then-boyfriend Scott Michael Foster.

She was cast as Alex Vause, a former drug importer and girlfriend of Piper Chapman (Schilling).

[32] In 2016, Prepon appeared in the psychological thriller The Girl on the Train, based on Paula Hawkins' novel of the same name.

[34] Prepon directed the tenth episode of Orange Is the New Black's fifth season, titled "The Reverse Midas Touch".