At 16, Fox made her acting debut in the 2001 film "Holiday in the Sun," as spoiled heiress Brianna Wallace and rival of Alex Stewart (Ashley Olsen). The film was released Direct-to-DVD on November 20, 2001. The following year, Fox landed the lead main role as Ione Star on the television series "Ocean Ave." The series lasted two seasons, from 2002–2003 and Fox appeared in 122 one-hour-long episodes. Also in 2002, she guest-starred on "What I Like About You," appearing in the episode "Like a Virgin (Kinda)." She was an uncredited extra in "Bad Boys II "in 2003. In 2004, Fox guest-starred on "Two and a Half Men" in the episode "Camel Filters and Pheromones." In the same year, Fox made her film debut in "Confessions of a Teenage Drama Queen" co-starring opposite Lindsay Lohan, playing the supporting role of Carla Santi, a rival of Lola (Lindsay Lohan). Again in 2004, Fox was cast in regular role on the ABC sitcom "Hope & Faith," in which she portrayed Sydney Shanowski, replacing Nicole Paggi in the role. Fox appeared in 36 episodes from seasons 2 to 3, until the show was cancelled in 2006.
In 2007, Fox won the lead female role of Mikaela Banes in the 2007 live-action film "Transformers," based on the toy and cartoon saga of the same name. Fox played the love interest of Shia LaBeouf's character Sam Witwicky. Fox was nominated for an MTV Movie Award in the category of "Breakthrough Performance." and was also nominated for three Teen Choice Awards, in the category of "Choice Movie Actress: Action Adventure," "Choice Movie: Breakout Female," and "Choice Movie: Liplock." Fox has signed on for two more "Transformers" sequels. In June 2007, Fox was cast in a minor role in "How to Lose Friends & Alienate People," starring alongside Jeff Bridges, Simon Pegg and Kirsten Dunst. She portrayed Sophie Maes, a love interest of Sydney Young (Simon Pegg). The film premiered on October 3, 2008, but was considered a box-office failure. In 2008, Fox appeared alongside Rumer Willis as the character Lost in "Whore." The film centers around a group of young hopeful teenagers who have come to Hollywood in the hopes of an acting career find that the business is harder than they had ever imagined. The film was released October 20, 2008.
Fox reprised her role as Mikaela Banes in the "Transformers" sequel, "Transformers: Revenge of the Fallen." There was some controversy surrounding Fox's appearance while filming the sequel of "Transformers" when Michael Bay, the movie's director, ordered the actress to gain 10 pounds. "Transformers: Revenge of the Fallen" premiered on June 8, 2009 in Tokyo, Japan. The movie was released worldwide on June 24, 2009. Fox had her first lead role playing the title character in "Jennifer's Body," written by Academy Award-winning screenwriter Diablo Cody. She played Jennifer Check, a mean-girl cheerleader possessed by a demon who begins to feed off the boys in a Minnesota farming town. The film was released on September 18, 2009 and co-stars Amanda Seyfried and Adam Brody.
In April, 2009 Fox began filming "Jonah Hex," in which she will portray Leila, a gun-wielding beauty and Jonah Hex's (Josh Brolin) love interest. The film, currently in production, is set to be released on June 18, 2010. The movie stars Josh Brolin and Will Arnett, and Fox described her role in the film as being a cameo. In early April, 2009 Fox signed on to star as the lead female role in the up-coming 2011 film "The Crossing" about a young couple who get caught up in a drug trafficking scheme during their vacation to Mexico. In March 2009 Variety reported that Fox was set to star as the lead role of Aspen Matthews in the film adaption of the comic books "Fathom" which she will also co-produce with Brian Austin Green. Fathom is currently in pre-production.