The son of Samuel and Mary Danforth and the younger brother of John Danforth, Samuel Danforth II was born in Roxbury, Massachusetts. Like his father and elder brother, he began writing poetry at Harvard, graduating in 1683, and entered the ministry, becoming pastor of the Congregational church at Taunton, Massachusetts, in 1688. In addition to serving as minister at Taunton, he ran a gristmill, taught Indian children, wrote an unpublished Indian dictionary (a portion of which is in the library of the Massachusetts Historical Society), and served as a lawyer and physician as well. On 4 October 1688, he married Hannah Allen of Boston. They had fourteen children, ten of whom outlived their father.

In "Ad Librum," the poem with which he introduced the almanac for 1686, Danforth attempted to read the signs placed by God throughout the universe and brought his own considerable knowledge of astronomy to bear on his reading. In his broadside An Elegy on the Memory of the Worshipful Major Thomas Leonard (1713), Danforth considered in detail Leonard's work as a doctor and lawyer in attempting to understand and articulate the religious significance of Leonard's life. Both poems are enlivened by his precise observations of a world that he saw as a book to be read carefully for the messages put there by its Maker. All contemporary accounts of his forty-one-year ministry in Taunton portray him as a man of great learning and considerable influence, especially with young people.