Mason showed an intense interest in music from childhood. He lived in Savannah, Georgia, for 15 years, working as a bank clerk, but pursuing his true love-music-on the side. He studied with F. I. Abel, improving his skills to the point where he began composing his own music. Numerous publishers in Philadelphia and Boston rejected his early work, until it was finally accepted in 1822 by the Handel and Haydn Society of Boston, Massachusetts, his native state. However, the collection did not even carry Mason's name:

I was then a bank officer in Savannah, and did not wish to be known as a musical man, as I had not the least thought of ever making music a profession.

Little did he know that "rejected" collection would eventually go through 17 editions (some sources say 21) and sell 50,000 copies. It was adopted by singing schools in New England, and eventually church choirs.

After seeing the success of his work, Mason returned to Boston in 1826. He also became the director of music at the Hanover, Green, and Park Street churches, alternating six months with each congregation. Finally, he made a permanent arrangement with the Bowdoin Street Church, though he still held his job as teller at the American Bank. Music continued to pull on him, though; he became president of the Handel and Haydn Society in 1827.

It was in Boston that Mason became the first music teacher in an American public school. In 1833, he co-founded the Boston Academy of Music; in 1838, he became music superintendent for the Boston school system. Lowell Mason wrote over 1,600 religious works, and is often called the "father of American church music." His works include:

• The Choir, or Union Collection of Church Music, 1832
• Union Hymns, with Rufus Babcock, Jr. (Boston, Massachusetts: 1834)
• Carmina Sacra: or Boston Collection of Church Music (Boston, Massachusetts: J. H. Wilkins & R. B. Carter, 1844)
• Cantica Laudis: or The American Book of Church Music (New York: Mason & Law, 1850), with George J. Webb
• Musical Letters from Abroad (Boston, Massachusetts: Oliver Ditson & Co., 1853)
• The New Carmina Sacra (Boston, Massachusetts: Rice and Kendall, 1853)
• The Hallelujah: A Book for the Service of Song in the House of the Lord (New York: Mason Bros., circa 1854)
• The Diapason: A Collection of Church Music, edited by George F. Root (New York : Mason Brothers, 1860)

Melodies for:

A Charge to Keep I Have

My Faith Looks Up to Thee
Nearer My God to Thee
Safely Through Another Week
Spirit of Faith Come Down
When I Survey the Wondrous Cross (Arrangement of melody)
Work for the Night Is Coming