She has appeared on Broadway and in theatre throughout her career. She attended the Professional Children's School in Manhattan.
For her role Martha Plimpton received a Primetime Emmy Award nomination for Outstanding Lead Actress in a Comedy Series in 2011. She first appeared as Jonsy in the feature film The River Rat (1984) before rising to prominence in the Richard Donner film The Goonies (1985) portraying the character Stef. Plimpton's role garnered her further success within the feature film industry.