He was a son of Robert Southwell (died 1598) of Woodrising, Norfolk, and Elizabeth Howard, eldest daughter of Charles Howard, 1st Earl of Nottingham, and a lady in waiting to Queen Elizabeth.
He sold the family estates to Francis Crane.
[1] Southwell married Margaret Fuller on 27 March 1618.
[2] Their children included: He came to live apart from his first wife in the company of Mary Eden, the daughter of a Doctor of Laws (presumably Thomas Eden LL.D.
Margaret Southwell complained in 1634 about his adultery and relationship with her sister.