Jessica Beatrice McGill Fletcher is a former high school English teacher who takes up writing mystery novels as a way of helping her cope with the sudden passing of her husband Frank. Frank's nephew Grady, who was raised by the Fletcher's following the death of his parents, finds one of Jessica's novels and submits it to a publisher behind her back. Not only does the novel get published, but it becomes a best seller. Soon Jessica becomes an international celebrity and travels throughout the United States and the world promoting her novels. However, she also displays a knack for solving murders and becomes a well respected amateur criminologist. She often solves crimes with the aid of her friends Dr. Seth Haslett and Sheriff Amos Tupper (and later former New York cop Sheriff Mort Metzger) and occasionally with other sleuths such as Boston private investigator Harry McGraw, Chicago private eye Charlie Garrett and reformed thief Dennis Stanton.

Angela Lansbury was the fourth choice to play Jessica Fletcher. Jean Stapleton was offered the part but turned it down, as did Doris Day.