Francis was born about 1589, the eldest son of Sir Percival and Bridget Willoughby of Wollaton. He spent the first ten years or so of his life at Middleton in Warwickshire, before the family moved to Wollaton Hall in Nottinghamshire in 1599. He was educated at Magdalen College Oxford (where he matriculated aged 17 on 26 June 1607), and was admitted to Lincoln's Inn in 1609.
He married Lady Cassandra Ridgway, daughter of Thomas Ridgway, 1st Earl of Londonderry, in 1610.
Francis lived at Middleton in Warwickshire, one of the manors inherited by his mother, from about 1615. Wollaton was damaged by fire late in his father's lifetime and he never returned to live there.
Francis died aged 67 on 7 December 1665 and was buried at Middleton. A large monument to him and Cassandra was constructed in the church.
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