Tutor and fellow of Harvard College, poet, astronomer, and for twenty-four years pastor of the church at Roxbury, Massachusetts, Samuel Danforth was born in Framlingham, Suffolk, England, the second son of Nicholas and Elizabeth Danforth. His mother died when he was three years old. He and his father immigrated to New England when he was eight. Though his expressions of shock when reciting from pagan poets to his Harvard tutor caused him to be thought unhealthily pious, he went on to graduate in 1643 and seems to have recovered well enough to fill his almanac for 1647 with poems modeled on Vergil and full of classical deities busily celebrating the circle of the seasons and the growth and beauty of New England.

In 1641 he was invited by the Reverend Mr. Thomas Welde to become colleague pastor of the church at Roxbury, there to serve with the Reverend Mr. John Eliot, whose missionary work among the Indians often took him away from his domestic ministry. Danforth accepted the call, was ordained on 24 September 1650, and served the Roxbury congregation for the rest of his life. On 5 November 1651 he married Mary Wilson of Boston. They had twelve children, many of whom died young. Two sons, John and Samuel II, became ministers and poets.

Something of his erudition and the quality of his mind can be gathered from his description and explanation of the comet that appeared at the turn of the years 1664-1665. Danforth argued that comets have natural causes, obey mathematical laws, and should therefore be studied scientifically by astronomers; they are also signs sent to man by God, carriers of divine portents, and therefore to be studied by theologians as well. Like his brother Thomas, a colonial governor, and his sons John and Samuel II, also well-known as poets and scientists as well as for their ministry, he took an active part in all affairs of New England, sacred and secular.