Fox also portrayed the titular character in the horror comedy Jennifer's Body (2009), starred as April O'Neil in the superhero action film Teenage Mutant Ninja Turtles (2014) and its sequel Teenage Mutant Ninja Turtles: Out of the Shadows (2016), and appeared in the fifth and sixth seasons of the Fox sitcom New Girl (2016–2017).

[16] She revealed in an interview that she developed an eating disorder in her adolescence and struggled with manic depression, the latter of which "[ran] in my family, so there was definitely some wrestling with chemical imbalance going on.

"[24] Fox also said that she was never popular in high school, and that "everyone hated me, and I was a total outcast, my friends were always guys, I have a very aggressive personality, and girls didn't like me for that.

"[24] In 2001, Fox made her acting debut in the romantic comedy Holiday in the Sun, as spoiled heiress Brianna Wallace and rival of Alex Stewart (Ashley Olsen), which was released direct-to-DVD on November 20, 2001.

She was also cast in a regular role on the ABC sitcom Hope & Faith, in which she portrayed Sydney Shanowski, replacing Nicole Paggi.

[25] 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.

She confessed on GQ Magazine that she had lost approximately 30 pounds during filming due to consuming a primary diet of water and vinegar,[citation needed] and reportedly had a dispute over her visible loss of weight with the director on set.

[32] In 2009, Fox had her first lead role since the Transformers series; she portrayed the title character in Jennifer's Body, written by Academy Award–winning screenwriter Diablo Cody.

"[42][43] Fox appeared with Dominic Monaghan in the music video for Eminem and Rihanna's single "Love the Way You Lie".

She voiced the role of Lois Lane in the animated comedy film Robot Chicken DC Comics Special,[45] an episode of the television comedy series Robot Chicken that aired as a one-off special during Cartoon Network's Adult Swim programming block on September 9, 2012.

[46] In February 2013, Fox set aside her differences with her former director Michael Bay and worked again with him on his reboot of Teenage Mutant Ninja Turtles (2014), starring as the lead human character of April O'Neil.

[54] In 2019, Fox starred in the mystery-fantasy film Above the Shadows opposite Olivia Thirlby and Alan Ritchson, directed by Claudia Myers.

[58] In 2020, Fox starred opposite Josh Duhamel in the family comedy film Think Like a Dog, which was released on video on demand on June 9, 2020.

[62] In 2022 Fox starred in the drama comedy Big Gold Brick, alongside Oscar Isaac, Andy García, Lucy Hale, and Emory Cohen, directed by Brian Petsos.

[63][64] Fox also played a role in the film Taurus, a musical drama, alongside Machine Gun Kelly, Naomi Wild, and Lil Tjay.

[67] Fox played Gina in the fourth Expendables film, Expend4bles, and voiced Nitara in the video game Mortal Kombat 1, both released in September of the same year.

"[2] Craig Flaster of MTV stated, "Transformers broke Fox into the mainstream, immediately turning her into a household name and international sex symbol.

[71][72] Scholar Marc DiPaolo stated that Fox achieved instant fame as Mikaela in Transformers because a "highly sexualized, erotically idealized figure draped over a car or motorcycle invariably evokes lust in the heterosexual male onlooker" and Fox did this by leaning over a Camaro while wearing "a flimsy pink belly shirt" and short skirt, which read as "an unequivocal sex invite" to male viewers.

[75][77] Scholars Wheeler Winston Dixon and Gwendolyn Audrey Foster disagreed that every woman in Hollywood is marketed as a sex symbol, and stated that Fox's "celebrity is based on what she admits is an entirely artificial construct designed for dissemination in the Internet age, a 21st-century media personality in every sense of the word.

"[75] Part of her persona included making outlandish comments,[77][78] which she said helped her reach her level of fame versus being "a typical starlet" who "said all the right things".

[88] DiPaolo concluded that Fox's criticism of the press's sexually objectifying girls and women was in stark contrast to her sex symbol status and that "her defiance of director Michael Bay and frequent outspoken comments" stifled her career.

[91] She considered being typecast as attractive an opportunity to surprise people when she gives a good performance in a film,[90][76] but said she is interested in portraying less sexualized characters.

"[97] Dixon and Foster stated, "The problem [Fox] faces is that the [image] construct has replaced the real in the minds of the public; and once established, a media persona is hard to recalibrate.

"[107] She has several tattoos, including the Chinese symbol for "strength" drawn on the back of her neck, a quote from the William Shakespeare play King Lear that reads "We will all laugh at gilded butterflies," the yin and yang symbol on her left wrist, and a crescent moon entwined with a star on her ankle.

Fox also has a poem tattooed near her breast that reads "There once was a little girl, who never knew love until a boy broke her heart" and another on her back that quotes Friedrich Nietzsche: "And those who were seen dancing were thought to be insane by those who could not hear the music."

She removed the portrait of Marilyn Monroe that was tattooed on her right forearm, stating "It is a negative character, as she suffered from personality disorders and was bipolar.

"[109][110] She also has a tattoo on her left collarbone that reads "the gunman" in Spanish, as well as numerous flowers and one snake on her abdomen.

[113] In her book Pretty Boys Are Poisonous, Fox revealed that she miscarried her pregnancy with what would have been her fourth child and her first with Machine Gun Kelly.

[115] Fox began dating actor Brian Austin Green in 2004, after meeting on the set of Hope & Faith; she was 18 years old and he was 30.

[116][117] According to Fox, Green was initially hesitant to enter a relationship with her due to the age difference, stating, "I had to convince him that I was slightly more responsible and well-spoken and had other things to bring to the table besides being 18."