Although she had acted in a couple of short films, Perabo was a virtual unknown when she landed the part in "Whiteboys,” but she quickly landed roles in two high profile summer 2000 releases. In the live-action/animation "The Adventures of Rocky and Bullwinkle", she was cast as a rookie FBI agent who teams with the title heroes to thwart the machinations of Fearless Leader and the No-Goodniks Boris Badenov and Natasha Fatale. Perabo followed with her first leading role as an aspiring singer-songwriter who moonlights as a bartender in the drama "Coyote Ugly.”
Continuing her ascent, she landed a key role in Lea Pool's "Lost and Delirious" (2001), about relationships among the residents of a private girls' school, and appeared in "Slap Her...She's French!" (2002) as Genevieve LePlouff, a French foreign-exchange student who comes to a small Texas high school, befriends a classmate, and practically takes over her life. The actress' next major film appearance was in the 2003 remake of the family comedy "Cheaper By the Dozen," playing Steve Martin and Bonnie Hunt's oldest daughter Nora, who's bedeviled by an obnoxious and vain boyfriend (Ashton Kutcher). The comedy was a runaway hit, taking in close to $140 million in domestic receipts.
After starring in the straight-to-video romantic comedy “Perfect Opposites” (2004), Perabo was the tomboy in a group of cave explorers that leads a pair of biologists into an elaborate cave system beneath the newly discovered ruins of a 13th century Romanian abbey in the sci-fi thriller, "The Cave" (2005). But instead of discovering an new ecosystem, as the biologists had hoped, the group finds a new species of unique and unwelcoming beings formed by the isolated environment. A clichéd storyline, unknown cast and lack of aggressive advertising ensured a $6 million opening weekend. Perabo next rejoined the original cast for the sequel “Cheaper By the Dozen 2” (2005), wherein Tom and Kate Baker (Martin and Hunt) try to bring their family together for a memorable summer vacation. Meanwhile, she was cast for a supporting role in “Because I Said So” (lensed 2005), a romantic comedy about a well-intentioned but overzealous mother who goes on a mission to find Mr. Right for her oldest and still unmarried daughter.