After her early success as a child actress, she returned to acting at age 18 as the character Deb in the 2004 film Napoleon Dynamite.

She has appeared in multiple television series, including Big Love, True Blood and Grey's Anatomy.

[10] From 2004 onward, she played a recurring role on UPN's series, Veronica Mars, as the computer-savvy Cindy "Mac" Mackenzie.

[11] During her time on Veronica Mars, she also started appearing in a recurring role on the cable television series Big Love with Waterworld costar Jeanne Tripplehorn and fellow Veronica Mars cast members Amanda Seyfried and Kyle Gallner.

She played the role of Addy Fisher, a meek, insecure first-year associate at a high-profile law firm.

In 2014 she appeared in the Veronica Mars film as her character Mac, a project financed by fans through Kickstarter.

[18] In an interview with Mental in 2022, Majorino talks about dealing with anxiety and how therapy, meditation, and setting boundaries has helped her finally find self-love.