A graduate of the University of Southern California, she had her breakthrough role as Spencer Hastings in the Freeform teen drama series Pretty Little Liars (2010–2017).

Her parents are producers Deborah Pratt and Donald P. Bellisario;[1] her father created Magnum, P.I., Quantum Leap, and NCIS, among other TV series.

[5][6] Attending Campbell Hall School in Studio City, California, from kindergarten through twelfth grade,[7] Bellisario was the valedictorian of her class.

[8] After high school, she attended Vassar College for several months before taking a break for the sake of her mental health, feeling that the institution aggravated her perfectionist tendencies.

Beginning in 2006, Bellisario began appearing in a number of independent short films namely, Unspoken, Archer House and Intersect.

[14] Bellisario also starred in Immediately Afterlife, a short film about two cult members who are the only survivors of their group's mass suicide, playing Bennett, alongside her Pretty Little Liars co-stars Shay Mitchell (Emily), Ian Harding (Ezra Fitz) and Nolan North (Peter Hastings).

In March 2020, Bellisario played the lead role of Claire in the CBS political drama pilot Ways & Means, written by Mike Murphy and Ed Redlich.

[22] The pilot, which also starred Patrick Dempsey, focused on a secret alliance between a disillusioned career politician and an idealist up-and-comer in the gridlocked American system.

[24] The film, produced by Chris Pine and directed by Cheryl Nichols, deals with Bellisario's character hiring her midwife's son as the latter's replacement when she passes away.