MacFarlane first started voicing characters on Hanna-Barbera shows including Johnny Bravo. Then after her work with Hanna-Barbera ended, MacFarlane began voicing many characters on Cartoon Network.
In addition to voice acting, Rachael has also been involved in other aspects of animation, such as being a production manager for The Grim Adventures of Billy & Mandy and Welcome to Eltingville, and wrote an episode of The Grim Adventures of Billy & Mandy, titled “Educating Grim” – where she also met her husband. Seth MacFarlane asked her to help him with his new pilot for the Fox Broadcasting Company, which would become Family Guy. She remained an incidental cast member on Family Guy for several years, as well as working for both The Walt Disney Company and Cartoon Network. In 2005, she was cast in American Dad!, where she voices Hayley Smith, protagonist Stan Smith’s rebellious teenage daughter.
MacFarlane also continues to contribute to Family Guy, on a regular basis. In September 2012, she released her first album Hayley Sings, which is a jazz vocal tribute to Hayley Smith, her character on American Dad!.
MacFarlane and her husband, Spencer Laudiero, have also published picture books for children.