With a resume boasting some impressive dramatic credits both on screen and in stage productions including "The Lights" at London's Royal Court Theatre and "The Merchant of Venice" at Edinburgh's Lyceum Theatre, Mortimer surprised audiences with her next career move. Playing Angelina Tyler in Wes Craven's "Scream 3" (2000) introduced the actress to an all new audience, and offered her the opportunity to play Neve Campbell's hard to kill Sidney in the horror-flick-within-a-horror-flick "Stab 3". While taking the role was an interesting and courageous move for the actress, many found her miscast or wasted in the thankless role. Next she was featured as Katherine in Kenneth Branagh's 1930s-set Busby Berkeley-esque musical take on the Shakespeare comedy "Love's Labour's Lost" (also 2000). While her acting was without fault, segments of the film that required her singing resulted in a discomfort in the actress that was apparent to the moviegoer. She fared better in that year's "Disney's The Kid,” playing Bruce Willis' feisty British love interest in a turn that showcased her luminous screen presence. Mortimer returned to period work with a featured role in the 1920s-set romantic comedy "Sleeping Dictionary" (also 2000) and followed up by co-starring with Nicolas Cage and Christian Slater in John Woo's "Windtalkers" (2001).

Mortimer did the best she could in the formulaic actioner “Formula 51” (2002), playing a detached, but abrasive hit-woman who locks horns with an American master chemist (Samuel L. Jackson) trying to make his last payday by introducing a designer drug to the European market. She stepped back from the action genre to settle into the ensemble comedy “Lovely & Amazing” (2002), then appeared in the straight-to-video period romance, “The Sleeping Dictionary” (2003). She gave a good performance as a young television journalist acting as a translator between two brothers (Tim Blake Nelson and David Arquette) and potential Russian brides in the dark comedy, “A Foreign Affair” (2003). Mortimer next appeared in the little seen “Young Adam” (2004), an erotic drama about a young drifter (Ewan McGregor) who engages in a passionate, but ultimately cruel relationship with a downtrodden woman (Tilda Swinton), all the while hiding a similar affair with another woman (Mortimer).

After some voiceover work for the American edition of the anime adventure, “Howl’s Moving Castle” (2004), she portrayed a young mom always on the move with her 9-year-old son (Jack McElhone) to avoid the boy’s abusive father in the heartwarming family drama, “Dear Frankie” (2004). A small part in the comedy of manners “Bright Young Things” (2004) was followed by an underutilized role in Woody Allen’s return to form, “Match Point” (2005), wherein she played the wife of an ex-tennis pro (Jonathan Rhys-Meyers) so consumed with getting pregnant that she fails to realize that he’s having a passionate affair with a struggling American actress (Scarlett Johansson). Mortimer was next set to appear in “The Pink Panther” (2006), the inexplicable remake starring Steve Martin as the bumbling Inspector Clouseau—a part once performed to perfection by the incomparable Peter Sellers.