Appleby began her acting career at the age of four, starting with advertisements for various products such as Cheerios and M&M’s. (1989), ER (1994), Baywatch (1989), Xena: Warrior Princess (1995), 7th Heaven (1997), Beverly Hills, 90210 (1990), before landing her break-out role in the series Roswell (1999–2002), where she tried out for the roles of Isabel and Maria before landing the leading role of Liz Parker.
She started acting and taking acting classes because her parents were concerned that she was so shy and introverted. In 2006, she had a recurring role on the short-lived ABC drama Six Degrees as Anya, a young assistant in a relationship with a much older photographer.
She had recurring roles on both the NBC drama series Chicago Fire and the HBO comedy-drama series Girls."I think it's just easier in the sense that it doesn't feel as unknown, as foreign," she said. Of course, the other question is 'How do you have two and juggle it and manage it?' but millions of people have done it before us so I feel like we'll figure it out.Aswell as having the lead role in Roswell High, Appleby has also appeared in rather large and recurring roles in shows such as E. She also appeared in the films Charlie Wilson's War, The Skin Horse, What Love is and Pizza my Heart.Her show, Life Unexpected, was confirmed for a second series, where she co-stars with Britt Robertson before it was cancelled.When she was only 4, she starting acting in national commercials.