He is best known for having written the lyrics to "My Country, 'Tis of Thee" (sung to the tune of "God Save the King"), which he entitled "America".

Smith attended Harvard College from 1825 to 1829, and was a classmate of William Henry Channing, James Freeman Clarke, Benjamin Robbins Curtis, George T. Davis, Oliver Wendell Holmes Sr., Isaac Edward Morse, Benjamin Peirce, George W. Richardson, and Charles Storer Storrow.

While a student at Andover Theological Seminary, Smith gave Lowell Mason lyrics he had written and the song was first performed in public on July 4, 1831, at a children's Independence Day celebration at Park Street Church in Boston.

Smith was foster father for four years to teenager Thornton Chase, who, instead of entering college, left to become an officer in the Civil War.

[4] Professor and author Oliver Wendell Holmes Sr. recommended Smith as a potential candidate for an honorary Doctor of Letters degree from Harvard University in 1893.

Harvard president Charles William Eliot declined, noting that "My Country 'Tis of Thee" was better known for its tune, which Smith did not write, rather than its lyrics.

"[5] Samuel Francis Smith died suddenly on November 16, 1895, while on his way by train to preach in the Boston neighborhood of Readville.