Born to Joshua Tomacham and his wife Sarah, Occom is believed to be a direct descendant of Uncas, the notable Mohegan chief. In 1743 at the age of 20, Occom heard the teachings of Christian evangelical preachers in the Great Awakening. He began to study theology at the "Lattin School" of Congregational minister Eleazar Wheelock in 1743 and stayed for four years until leaving to begin his own career. In addition to improving his English, Occom learned to read and speak Hebrew. As a young man, the only book he owned was the Bible. From 1747 until 1749, Occum worked under and studied with the Reverend Solomon Williams in New London, Connecticut.
Occom became a teacher, preacher, and judge to Pequot Native Americans in Montauk, eastern Long Island. He married Mary Fowler, a local woman. Occom helped the Pequot to assimilate and adopt European-style houses, dress and culture. He was officially ordained a minister on August 30, 1759, by the presbytery of Suffolk. Occom was never paid the same salary as white preachers, although promised that he would be. The "Society in Scotland for Propagating Christian Knowledge" also gave Occom a stipend, but he lived in deep poverty for much of his life. In 1761 and 1763, Occom traveled to the Six Nations of the Iroquois in upstate New York to preach. Winning few converts, he returned to teach at Mohegan, Connecticut, near New London.
Meanwhile, in 1754, Wheelock had established an Indian charity school in Lebanon, Connecticut, with a legacy from Joshua Moor, among others. Wheelock persuaded his former pupil to travel to England to raise money for the school. Occom preached his way across Britain from February 16, 1766, to July 22, 1767, delivering between three and four hundred sermons, drawing large crowds wherever he went, and raising over ₤12,000 (pounds) for Wheelock's project. King George III donated 200 pounds, and William Legge, Earl of Dartmouth, subscribed 50 guineas. However, Occom on his return learned that Wheelock had failed to care for Occom's wife and children while he was away. Furthermore, Wheelock moved to New Hampshire and used the funds raised to establish Dartmouth College (named after the generous aristocrat) for the education of Englishmen, rather than Native Americans as originally promised to Occom.
In 1768, Occom wrote the 10-page A Short Narrative of My Life, a manuscript now held in Dartmouth College's archive collection; it was first published in 1982. The document expands upon a single page biography that Occom wrote before his preaching tour of England and Scotland. Occom also published Sermon at the Execution of Moses Paul and A Choice Collection of Hymns and Spiritual Songs in 1774. All provide a very different perspective on the relations between colonists and Native Americans from Mary Rowlandson's narrative of her captivity in similar areas a century earlier.
Upon his return from England, Occom lived with the Mohegan people. After Wheelock's betrayal, Occom worked to organize Christianized Indians of New England and Long Island into a new tribe, located in western Connecticut. Under continuing pressure from settlers following the American Revolutionary War, in 1785 they migrated at the invitation of Christians of the Oneida tribe to their reservation in central New York state. Occom, his son-in-law Joseph Johnson (Mohegan) (a messenger for General George Washington during the American Revolution), and his brother-in-law David Fowler (Montauk) led the emigrants who built a new settlement called "Brothertown" (originally nearby Waterville, New York). The Oneida also invited other Christian Indians to live with them, namely the Stockbridge Mohican from western Massachusetts and two Lenape groups from southern New Jersey. The Mohicans founded what they called New Stockbridge in New York, near Oneida Lake. Occom not only assured that these villages received civil charters in 1787, but also evicted white settlers from Brothertown on April 12, 1792.
Occom died on July 14, 1792, in New Stockbridge. He is buried just off Bogusville Hill Road outside of Deansboro.
In the 1820s, many Brothertown Indians and some Oneida accepted payment for their land from New York State and removed to what is now known as the town of Brothertown in Calumet County, Wisconsin. In the modern era, the Brothertown Indians petitioned the federal government for recognition as a tribe, but were denied and have appealed.
In World War II, the United States liberty ship SS Samson Occom was named in his honor.
Several locations around Dartmouth College in Hanover, New Hampshire, are named after Occom, including Occom Pond and Occom Ridge on the college campus' northern edge. Bruce Duthu is the Samson Occom Professor and Chair of Native American Studies Program. The Occom Commons community space is part of Goldstein Hall, in the recently opened McLaughlin Residential Cluster. Eastern Connecticut State University in Willimantic, Connecticut, also named a residence hall for upperclassmen after Occom.
The Norwich, Connecticut neighborhood of Occum is named for Samson Occom.
Occom is honored with a feast day on the liturgical calendar of the Episcopal Church (USA) on July 14.A Choice Collection of Hymns and Spiritual Songs, New London, Connecticut: Press of Thomas and Samual Green, 1774.A Sermon Preached at the Execution of Moses Paul, An Indian Who Was Executed at New Haven on the 2nd of September 1772 for the Murder of Mr. Moses Cook, late of Waterbury, on the 7th of December 1771, New Haven: Press of Thomas and Samual Green, 1772."A Short Narrative of My Life". The Elders Wrote: An Anthology of Early Prose by North American Indians 1768-1931. Ed. Bernd Peyer. Berlin: Dietrich Reimer Verlag, 1982 , 12-18. (This work has recently been published in The Norton Anthology of American Literature.)Journals, 1754 and 1786(?), Unpublished manuscript in collection of New London County Historical Society.Herbs and Roots, Unpublished manuscript in collection of New London County Historical Society.The Collected Writings of Samson Occom, Mohegan. Ed. Joanna Brooks. New York: Oxford University Press, 2006.