At the age of 14, Cook began auditioning for acting work. Her modeling agency sent her to read for a short film, 26 Summer Street (1996). She first gained national attention when she was featured in a This Is Your Brain on Drugs public-service television advertisement, in which she proceeds to destroy a kitchen with a frying pan as she lists the things that heroin harms (in 1998). Cook made her debut as an actress in the 1995 film The Baby-Sitters Club, which was based on Ann M. Martin's book series of the same name. Her second movie role was in Tom and Huck, where she portrayed Rebecca "Becky" Thatcher.
Cook has provided the voice of Tifa Lockhart in the video games Kingdom Hearts II and Dirge of Cerberus: Final Fantasy VII, as well as the CG movie Final Fantasy VII Advent Children. One of Cook's latest voice-over role is for the video game Yakuza where she voices the role of Reina, a beautiful barkeep. She also lent her voice to several episodes of Robot Chicken.
In 2009, Rachael joined the cast of Titan Maximum as the lovable Jodi.