He was born in Lancaster County, Pennsylvania to plantation owner John Groff and Susan Beaver (née Susan de Bouvoir) and married Julia Page Quick, the daughter of the Anglican Bishop of Philadelphia in Germantown, Pennsylvania on 14 March 1888.
In 1890 during a period of strong industrial growth, he relocated to Amherst, Massachusetts in order to develop what was at the time a large-scale farming enterprise. Despite the Great Depression, his enterprise fared exceptionally well compared to others, and he soon became a major landowner in Amherst. Upon reaching retirement age, he downscaled his holdings and donated large portions to the City of Amherst and to Amherst College.
Ulysses Grant Groff died in an automobile accident in Massachusetts two weeks before his 85th birthday.
He was the father of real estate developer and businessman Charles Wister Groff.