The daughter of a special agent with the FBI who uncovered Russian espionage during the Cold War and, later, worked on kidnapping and extortion cases, Clark's interest in suspense started at an early age. She attended high school at the Immaculate Heart Academy, in Washington Township, Bergen County, New Jersey, graduating in 1972. With the goal of working in television news, she graduated from the University of Rhode Island with degrees in journalism and political science. She started her professional career as a desk assistant at CBS News headquarters in New York City, eventually becoming a producer and writer.

Clark resides in the New York City area and Florida. She has two children, a daughter, Elizabeth, an actress, and a son, David who has Fragile X Syndrome, the most common inherited form of developmental disability. Mary Jane supports the FRAXA Research Foundation, a non-profit organization that supports scientific research aimed at finding a treatment or a cure for the condition.

Clark's former mother-in-law is the well-known American author Mary Higgins Clark. Mary Jane Clark's Frequently Asked Questions