The 5th Baron was the eldest son of Thomas Willoughby, younger brother of the 2nd Baron Middleton , and his wife Elizabeth Southby of Birdsall near Malton, Yorkshire. He was born at York, and entered Jesus College, Cambridge, in 1745. He served as High Sheriff of Yorkshire in 1757. He succeeded his cousin to the Middleton barony and estates in 1781, and died on 14 June 1800.
He married Dorothy, daughter and co-heir of George Cartwright of Ossington, Nottinghamshire, in 1756 (d 1808), and had:
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