Born to Don and Libby Matlin, a Jewish couple from Morton Grove, Illinois, Matlin lost most of her hearing at the age of 18 months, following a bout of Roseola infantum. She lost all hearing in her right ear, and 80f hearing in her left ear.

She made her stage debut at the age of seven, as Dorothy in a children's theatre version of The Wizard of Oz, and continued to appear with the same children's theatre group throughout her childhood.

Her film debut, 1986's Children of a Lesser God brought her a Golden Globe Award for Best Actress in a Drama and an Academy Award for Best Actress (at 21, the youngest person ever to receive the award.)

She played the lead female role in the television series Reasonable Doubts (1991 - 1993), and won an Emmy Award for an appearance in Picket Fences.

She had recurring roles in The West Wing and Blue's Clues. Other television appearances include Seinfeld and Law & Order: Special Victims Unit. She won a 2004 Primetime Emmy Award for the latter.

She is actively involved with a number of charitable organisations, including the Children Affected by AIDS Foundation, Elizabeth Glaser Pediatric AIDS Foundation, Starlight Children's Foundation, Red Cross Celebrity Cabinet, etc.

Matlin married law enforcement officer, Kevin Grandalski, a Roman Catholic, on August 29, 1993 (in Henry Winkler's back yard). They have two daughters (Sarah Rose, born 1996; Isabella Jane, born 2003) and two sons (Brandon, born 2000; Tyler, born 2002).

In 2002, she published her first novel, Deaf Child Crossing, which is loosely based on her own childhood.

In 2004, she starred in the controversial movie What the Bleep Do We Know as Amanda.