Hannigan got her start in television starring in the short-lived sitcom Free Spirit from 1989 to 1990, for which she earned a Young Artist Award nomination.

Hannigan hosted the television show Penn & Teller: Fool Us (2016–2023), and provided the voice of Claire Clancy in the Disney Junior animated series Fancy Nancy (2018–2022).

[8] Living with her mother and attending North Hollywood High School, she successfully auditioned for agents while visiting her father in Santa Barbara.

After high school, she attended California State University, Northridge, where she was a member of the Alpha Chi Omega sorority and earned a degree in psychology.

[11] The show became a success, and Hannigan gained recognition, subsequently appearing in several films aimed at teenage audiences, including Boys and Girls (2000).

[12] In 2017, Forbes reported that the American Pie films have grossed $989.5 million at the worldwide box office, and became a pop culture phenomenon.

In early 2004, Hannigan made her West End debut, starring in a stage adaptation of When Harry Met Sally... at the Theatre Royal Haymarket, opposite Luke Perry.

In September 2005, Hannigan returned to starring in a regular television series, taking the main role of Lily Aldrin in CBS' sitcom How I Met Your Mother.

Hannigan's character Lily was a kindergarten teacher and amateur painter, who eventually married lawyer Marshall Eriksen, portrayed by Jason Segel.

[25][26] Hannigan married her Buffy the Vampire Slayer and Angel co-star Alexis Denisof at Two Bunch Palms Resort in Desert Hot Springs, California, on October 11, 2003.