Samuel Stone traveled with John Cotton and Thomas Hooker to Boston in 1633 and became one of the leading clergymen in early New England. He was born at Hertford, England, the son of John Stone, and educated at Emmanuel College, Cambridge. On 13 June 1627 he was appointed curate at Stisted, Essex, where he remained until 13 September 1630, when he was suspended for nonconformity and sought refuge in New England. Hooker persuaded Stone to join him as an associate in a church at Newtown (now Cambridge) in New England, where they presided together nearly three years. In 1636 both Hooker and Stone moved to establish a new church in Hartford, Connecticut, a town named after Stone's birthplace in England. According to John Winthrop's History of New England (1853), Stone also served as chaplain under John Mason in the war against the Pequots in 1637. After Hooker's death in 1647, Stone continued as pastor of the Hartford church until his death in 1663.

Known for his ready wit and pleasant personality, Stone nevertheless became involved in a bitter dispute with a ruling elder over doctrinal differences, mainly the Half-Way Covenant, which caused a split in the church membership in 1659. He published one poem, an elegy for Thomas Hooker which was prefixed to Hooker's A Survey of the Summe of Church-Discipline ... (1648) and one sermon. A Congregational Church is a Catholike Visible Church. Or an Examination of M. Hudson ... (1652). In addition, he left two unpublished manuscripts, "Confutation of the Antinomians" and "A Body of Divinity," the latter called "a rich treasure" by Cotton Mather.