Dushku came to the attention of casting agents when she was 10. She was chosen at the end of a five month search throughout the United States for the lead role of Alice, playing with Juliette Lewis in the film That Night. In 1993, Dushku landed a role as Pearl alongside Robert De Niro and Leonardo DiCaprio in This Boy's Life, a role that she said opened a lot of doors. The following year, she played the teenage daughter of Arnold Schwarzenegger and Jamie Lee Curtis in True Lies. She also had parts as Paul Reiser's daughter in Bye Bye, Love, as Cindy Johnson with Halle Berry and Jim Belushi in Race the Sun, as well as roles in a television movie and a short film.
Dushku took some time off from acting to finish her junior and senior years of high school. She was accepted to the George Washington University in Washington, DC and Suffolk University in Boston, where her mother serves as professor of government and previously served as dean of the campus in Dakar, Senegal.