He was born in County Armagh, Ireland, in 1757, the son of John Humphreys and Margaret Carlisle.
In 1783, he emigrated to Augusta County, Virginia, and settled at Greenville near his brother, David Carlisle Humphreys.
He became a Justice of Augusta County and a Trustee of the newly created Staunton Academy in 1792.
Senator from Kentucky who served as President pro tempore of the U.S. Senate (and the father of Mason Brown, the Secretary of State of Kentucky, and Orlando Brown, the publisher and historian).
His widow, Mary, then moved to Frankfort, Kentucky, to be near her brother John Brown.