Clark began writing at an early age. After several years working as a secretary and copy editor, Clark spent a year as a stewardess for Pan-American Airlines before leaving her job to marry and start a family. She supplemented the family's income by writing short stories. After her husband died in 1959, Clark worked for many years writing four-minute radio scripts, until her agent convinced her to try writing novels. Her debut novel, a fictionalized account of the life of George Washington, did not sell well, and she decided to leverage her love of mystery/suspense novels. Her suspense novels became very popular, and as of 2007 her books have sold more than 80 million copies in the United States alone.
Her daughter, Carol Higgins Clark, is also a suspense writer.