In 1993, Dushku landed a role as Pearl, alongside Robert De Niro and Leonardo DiCaprio, in the drama film This Boy's Life.

The following year, she played the teenage daughter of Arnold Schwarzenegger and Jamie Lee Curtis in the action spy film True Lies.

Dushku planned to attend Suffolk University in Boston, where her mother taught,[11][16] but her agent asked her to submit a videotape audition for a television show starring another of his clients, Sarah Michelle Gellar.

After reading the script, Dushku rushed to a local Claire's to purchase dark makeup and other appropriate accessories for the part of Faith on Buffy the Vampire Slayer.

In 2001, she appeared in The New Guy with DJ Qualls and in City by the Sea with Robert De Niro and James Franco.

The same year, Kevin Smith invited Dushku to be a part of Jay and Silent Bob Strike Back.

After having a grant withdrawn, Tru is forced to take a job at a local morgue, where she discovers her power to "re-live" the previous day over again if one of the deceased asks for her help to change what has happened.

In an interview with Maxim in May 2001, Dushku says of her roles, "It's easy to play a bad girl: You just do everything you've been told not to do, and you don't have to deal with the consequences, because it's only acting.

On October 1, 2005, she announced at Wizard World Boston that shooting had begun for Nobel Son in which she would star with Alan Rickman, Danny DeVito, and Bill Pullman.

She voiced the role of Yumi Sawamura in the English-language version of Yakuza for the PlayStation 2, which was published and developed by Sega, and released in September 2006.

Dushku also stars as Shaundi, one of the lead characters in Saints Row 2, which was developed by Volition, Inc. and published by THQ.

Variety announced on August 2, 2006, that Dushku would co-star with Macaulay Culkin in Sex and Breakfast, a dark comedy written and directed by Miles Brandman.

She played the main character in The Thacker Case and The Alphabet Killer, both thrillers based on real-life events, one of them directed by Rob Schmidt, with whom she had worked on Wrong Turn.

[28] Subsequently, it was announced on October 31 that Dushku had lured Joss Whedon, of Buffy the Vampire Slayer, back to TV, to create a television series called Dollhouse.

The producers cited their confidence in the strength of Whedon's fan base and high DVR numbers as their reasons for keeping the show.

Dushku was the voice actor for contract killer "Rubi Malone" in the action video game Wet.

[34] In 2011, Dushku featured alongside Jayson Floyd in "One Shot", a short action clip on YouTube directed by and starring Freddie Wong, released on May 13, 2011.

[36] In June 2012, Dushku starred with Katie Cassidy, Gina Gershon and Michelle Trachtenberg in The Scribbler, directed by John Suits and produced by Gabriel Cowan.

Eventually she enlisted the help of Ondi Timoner[4] and Mapplethorpe, with Matt Smith as the title character, was brought to the screen in 2018.

[50] Dushku lived for more than 15 years in Los Angeles, though spending substantial time back in Watertown and Boston in the period before her stepfather died.

[55] Dushku began dating former Boston Celtics and Los Angeles Lakers basketball player Rick Fox in October 2009, and in August 2010 the couple confirmed that they were living together.

[citation needed] As a role model to campus leaders for her activism, Dushku was invited by the Millennium Campus Network (MCN) as a national keynote speaker and honored as a Global Generation Award winner alongside U.S. Secretary of State John Kerry at MCN events in 2011.

[51][68] Dushku visited her father's family and their home city in Albania in 2006 after receiving an invitation from Albanian Prime Minister Sali Berisha.

In January 2018, Dushku publicly alleged having been molested by stunt coordinator Joel Kramer when she was 12 and working on True Lies.

[74] In January 2019, CBS made a $9.5 million settlement with Dushku after she was fired from a recurring role on Bull, after informing producers of series lead Michael Weatherly's alleged inappropriate behavior on the set.

[75] According to documents from the official mediation, Weatherly was recorded on video making comments about spanking Dushku over his knee, soliciting a threesome, alluding to sexual assault in his "rape van", and other harassing statements.

"[76] Days later, showrunner Glenn Caron terminated Dushku's expected role on the show, despite opposition from studio executives.

Dushku responded that Weatherly broke the terms of their settlement by speaking to the press and characterized his apology as "more deflection, denial, and spin".

[76] In November 2021, Dushku testified in front of the House Judiciary Committee about her sexual harassment accusations during her time on Bull.

[77] In February 2021, Dushku shared a message of support for Charisma Carpenter, in reference to allegations of abuse against Buffy creator Joss Whedon.