She is best known for her role as Letha Godfrey on the first season of the Netflix series Hemlock Grove.
Born in Melbourne, Australia to a French-born artist mother and Australian entrepreneur father, Mitchell spent most of her childhood in Australia with her two older brothers. She studied ballet from age four to sixteen.
Mitchell finished in the top 1% of her graduating year, with an International Baccalaureate diploma. She attended Melbourne University, with the intention of becoming a lawyer. During her time there, she continued to perform and wrote prolifically for various publications. Mitchell completed her Bachelor of Arts degree in Media Communication before moving to Los Angeles to pursue acting.
She began acting a few years before she landed her role as Letha Godfrey on Hemlock Grove, appearing on several other shows, including Toon Time, an Australian kids show; the ABC (Australia) show Next Stop Hollywood, which followed six Australian actors (including Penelope) who move to Hollywood to audition for pilots; and an episode of Australian police drama Rush. In 2013, Mitchell was cast as Olivia Parker, a witch and member of the Gemini Coven on The Vampire Diaries, and she remained a recurring character throughout Seasons Five and Six. However, her character was killed off in the Season Six finale I'm Thinking Of You All The While.
- Penelope is the cousin of actress Radha Mitchell.