Samuel’s father was a member of the U.S. House of Representatives. His mother was a descendant of the John Alden and Priscilla of his brother Henry Wadsworth Longfellow's Courtship of Miles Standish. In college began his lifelong friendship with Edward Everett Hale, and in Divinity School began his long collaboration with his fellow hymn writer Samuel Johnson. Their Book of Hymns Theodore Parker called the “Sam Book,” which joyfully celebrated God’s being really present with us.

After preaching his first two sermons—for which he received two dollars—he was ordained and served in Fall River, Massachusetts and then in Brooklyn, New York, where his innovation of vesper services was the occasion for his writing the long beloved hymns, ”Now on Land and Sea Descending” and “Again as Evening Shadows Fall.”

In addition to his composing various poems, hymns, and essays, Samuel wrote the Life of Henry Wadsworth Longfellow.