The square was developed by 4th Earl of Southampton, in the late 17th century, and was initially known as Southampton Square.
In 1669, the Bloomsbury Estate came into ownership of the Russell family when William, son of William Russell, 1st Duke and 5th Earl of Bedford (1616–1700), married Lady Rachel Vaughan, one of the daughters of Thomas Wriothesley, 4th Earl of Southampton (1607–1667).
Southampton is a character in Hilary Mantel's novels on Thomas Cromwell, Wolf Hall and Bring Up the Bodies, (nicknamed Call-Me Risley for the pronunciation of the family name), and in Margaret George's novel, The Autobiography of Henry VIII
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After the dissolution of the monasteries in the 1540s, the manor was acquired by Thomas Wriothesley, Earl of Southampton.
Catherine's family play a key role including her sister Anne Parr Herbert, her stepdaughter Elizabeth, niece Jane Grey, doomed friend Anne Askew, rivals Thomas Wriothesley, Stephen Gardiner, Henry Howard, Anne Stanhope, Mary Howard Fitzroy the Dowager Duchess of Richmond and former romantic interest Thomas Seymour.