Murphy also voiced Luanne Platter on the animated television series King of the Hill (1997–2009).Her final film, Something Wicked, was released in April 2014.She began the 2000s with a leading role in Don't Say a Word (2001) alongside Michael Douglas; the TV adaptation of the novel The Devil's Arithmetic (2001); 8 Mile (2002), for which she received critical acclaim; and Uptown Girls (2003).
She also had recurring roles on Sister, Sister, Party of Five and Boy Meets World.
Murphy's breakthrough role was in her second feature film, the teen comedy Clueless (1995), directed by Amy Heckerling, which went on to receive cult status.
She returned to voice acting with the critically acclaimed 2006 animated feature Happy Feet, as Gloria Penguin.
In 2009, she was cast in the Lifetime TV movie Tribute, as the main character, Cilla.
The 2000s saw Murphy with roles in Don't Say a Word (2001) alongside Michael Douglas, and alongside Eminem in 8 Mile (2002), for which she gained critical recognition.
Her later roles included Riding in Cars with Boys (2001), Spun (2002), Uptown Girls (2003), Sin City (2005), and Happy Feet (2006).
Murphy denied media reports that she had been fired from the project after being difficult on set, and cited "creative differences".
Something Wicked, her final film, was released in 2014. She commented: "My singing voice isn't like my speaking voice...
She also voiced the character Luanne Platter on Fox's animated sitcom King of the Hill for the entirety of the show's run from 1997 to 2009, and Joseph Gribble until the fifth season.