She had a large role in the film The Hot Chick, alongside Rob Schneider, but her career really took off when she starred as "Regina George", "queen-bee" and the resident bitch of her school, in the 2004 hit Mean Girls. She starred opposite Hollywood It-Girl Lindsay Lohan. McAdams was told to partly model the character of Regina George after Alec Baldwin's performance in Glengarry Glen Ross (1992). Mean Girls got McAdams's name into many homes in the United States, and she won rave reviews for her performance.
McAdams had previously appeared in the Canadian television series "Slings and Arrows", alongside Paul Gross. She played a main role in the first season, but due to her rising stardom was written out of the second season, appearing in only the first episode.
She followed Mean Girls with the film adaptation of Nicholas Sparks' novel The Notebook, alongside Ryan Gosling. The pair would later continue their on-screen romance, rumoured to have started after they shared a passionate kiss onstage when accepting the MTV movie award for "best kiss."
McAdams was nominated for a Genie Award, the Canadian equivalent of the Academy Award, for her role in Perfect Pie. She was also nominated for the BAFTA's Orange Rising Star award which acknowledges the new talents in the acting industry. The award went to James McAvoy.
She hosted Academy of Motion Picture Arts and Sciences's 2006 Scientific and Technical Awards. McAdams received a Civic Award for her contribution to culture from the city of St. Thomas in 2006.