Ephraim was born in Deerfield, Massachusetts. He lived in nearby Hatfield for a while and settled in Stockbridge, Massachusetts, where he founded Williams College. He never married. Ephraim was a soldier, having served in King George's War (1744-1748) and the French and Indian War (1754-1763). He died in action near Lake George, New York.
In 1750, Ephraim sold a young boy named Prince to his cousin, Israel Williams. In 1755, soon before his death, he purchased a teenaged boy named J. Romanoo. In his will, dated that same year, Ephraim left his "Negro Servants" to his brothers, Joshua and Elijah.
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