Fox was diagnosed with Parkinson's Disease in 1991, and disclosed his condition to the public in 1998. Fox semi-retired from acting in 2000 as the symptoms of his disease worsened. He has since become an advocate for research toward finding a cure. This led him to create the Michael J. Fox Foundation, and on March 5, 2010, Sweden's Karolinska Institutet gave him a honoris causa doctorate for his work in advocating a cure for Parkinson's disease.

Since the year 2000 Fox has mainly worked as a voice over actor in films such as Stuart Little, and taken minor TV roles such as in Boston Legal and Scrubs. He has also released three books, Lucky Man: A Memoir (2002), Always Looking Up: The Adventures of an Incurable Optimist (2009) and A Funny Thing Happened on the Way to the Future: Twists and Turns and Lessons Learned (2010). He was appointed an Officer of the Order of Canada in 2010.

Michael Andrew Fox was born in Edmonton, Alberta, Canada, the son of Phyllis (née Piper), an actress and payroll clerk, and William Fox, a police officer and member of the Canadian Forces. Fox's family lived in various cities and towns across Canada because of his father's career. The family finally settled in the Vancouver suburb of Burnaby, British Columbia, when his father retired in 1971. Fox attended Burnaby Central Secondary School, and now has a theatre named after him in Burnaby South Secondary.

Fox co-starred in the Canadian television series Leo and Me at the age of fifteen, and in 1979, moved to Los Angeles to pursue an acting career at the age of eighteen. He was discovered by producer Ronald Shedlo and made his American television debut in the television movie Letters from Frank, credited under the name "Michael Fox". He intended to continue to use the name, but when he registered with the Screen Actors Guild, which does not allow duplicate registration names to avoid credit ambiguities, he discovered that Michael Fox, a veteran character actor, was already registered under the name. As he explained in his autobiography, Lucky Man: A Memoir, and in interviews, he needed to come up with a different name. He did not like the sound of "Andrew" or "Andy" Fox, so he decided to adopt a new middle initial and settled on "J", in reference to actor Michael J. Pollard.

Fox’s first feature film role was in Midnight Madness (1980) credited as Michael Fox. After this he played "Young Republican" Alex P. Keaton in the show Family Ties which aired on NBC for seven seasons, from 1982 to 1989. Fox only received the role after Matthew Broderick was unavailable. Family Ties had been sold to the television network using the pitch "hip parents, square kids," with the parents originally intended to be the main characters. However, the positive reaction to Fox's performance led to his character becoming the focus of the show following the fourth episode. At its peak, the audience for Family Ties drew one-third of America's households every week.

Brandon Tartikoff, one of the show's producers, felt that Fox was too short in relation to the actors playing his parents, and tried to have him replaced. Tartikoff reportedly said that "this is not the kind of face you'll ever find on a lunch-box". After his later successes, Fox presented Tartikoff with a custom-made lunch-box with the inscription "To Brandon, this is for you to put your crow in. Love and Kisses, Michael J. Fox". Tartikoff kept the lunch-box in his office for the rest of his NBC career.

While filming Family Ties, Fox met his future wife, Tracy Pollan when she portrayed his girlfriend, Ellen. When Fox left the TV series Spin City, his final episodes made numerous allusions to Family Ties: Michael Gross (who played Alex's father Steven) portrays Mike Flaherty's (Fox) therapist, and there is a reference to an off-screen character named "Mallory". Also, when Flaherty becomes an environmental lobbyist in Washington D.C., he meets a conservative senator from Ohio named Alex P. Keaton, and in one episode Meredith Baxter played Mike's mother.

Eric Stoltz was already filming Back to the Future when Robert Zemeckis, the director, felt that Stoltz was not giving the right type of performance for the humor involved. Zemeckis quickly replaced Stoltz with Fox. During filming, Fox would rehearse for Family Ties from 10 a.m. to 6 p.m, then rush to the Back to the Future set where he would rehearse and shoot until 2:30 a.m. This schedule lasted for two full months. Back to the Future spent 8 consecutive weekends as the number one grossing movie at the US box office in 1985, and eventually earned a worldwide total of $381.11 million. Two sequels, Back to the Future Part II and Back to the Future Part III were released in 1989 and 1990, respectively.

During and immediately after the Back to the Future Trilogy, Fox starred in Teen Wolf (1985), Light of Day (1987), The Secret of My Success (1987), Bright Lights, Big City (1988) and Casualties of War, (1989). In The Secret of My Success, Fox played a graduate student from Kansas State University who moves to New York City where he has landed a job as a financier. During the shooting of Bright Lights, Big City, Michael was reunited with his on-screen girlfriend Tracy Pollan from Family Ties. Fox then starred in Casualties of War, a war drama about the Vietnam War, alongside Sean Penn. Casualties of War was not a box office hit, but Fox, playing a Private serving in Vietnam, received good reviews for his performance.

In 1991, he starred in Doc Hollywood, a romantic comedy about a talented medical doctor who decides to become a plastic surgeon. While relocating from Washington D.C. to Los Angeles, California, he winds up as a doctor in a small southern town. The Hard Way was also released in 1991, with Fox playing an undercover actor learning from police officer James Woods. Between 1992 and 1996, he continued making several films, such as For Love or Money (1993), Life With Mikey (1993), Greedy (1994), The American President (1995), and Mars Attacks! (1996). His last major film role was in The Frighteners (1996).