Born in Justice Town, near Carlisle, England, Thomas Story was educated at the Carlisle Grammar School and read law under Dr. Richard Gilpin in Cumberland. Beginning in 1687 he practiced law in Carlisle. At about the same time he began to question the Church of England's rites, especially the practice of christening infants. On 1 April 1689, influenced by the many prominent Quaker families in the area, Story experienced a "conversion" to their beliefs and began to preach in 1693, the same year he met William Penn. When in 1695 Story decided to settle in London, Penn assisted him in finding employment as registrar of the Society of Friends.

Story accompanied Penn to Ireland in 1698. In November of the same year he immigrated to Pennsylvania, ultimately remaining there for sixteen years. He became the first recorder of Philadelphia, a member of the council of state, keeper of the great seal, master of the rolls, and in 1706 was elected mayor of Philadelphia, but declined to serve. He married Ann Shippen (circa 1706), who died about six years later. During this same period Story was accused of unfair and corrupt practices in his capacity as treasurer of the Pennsylvania Land Company, but he was ultimately cleared of criminal conduct by a London court of arbitration. In 1714 Story left Pennsylvania and the New World, apparently for good. During the remaining years of his life he traveled throughout Great Britain and Ireland preaching, debating theology, and bearing witness to his faith.

Story's major literary production was his autobiographical journal, published in full as A Journal of the Life of Thomas Story (1747) and in an abridged edition as The Life of Thomas Story (1786). In it he details the formative religious experiences of his conversion to the Quaker religion and gives accounts of his experiences preaching in Britain, Europe, and America. Providing fascinating details of his missionary labors and remarkable interviews with people of interest, Story offers important insights to the activities of the Society of Friends during the late seventeenth and early eighteenth centuries and his association with William Penn. The journal is fundamentally oriented toward recording "the tender mercies and judgments of the Lord" and the effects of this relationship upon the course of Story's life. It is a model of the religious autobiographical journal of his time.