Only son of Rt. Hon. William Russell, Lord Russell, and Lady Rachel Wriothesley. Paternal grandson of William Russell, 1st Duke of Bedford, and Lady Anne Carr. Maternal grandson of Thomas Wriothesley, 4th Earl of Southampton, and Rachel de Massue.
Wriothesley married Elizabeth Howland in 1695, who was a rich heiress and the daughter of John Howland of Streatham. His grandfather the Duke of Bedford, was created Baron Howland shortly after their marriage, with special remainder to Wriothesley and his heirs.
Six children were born of the marriage, with their first two sons dying in infancy. Of the remaining children, both surviving sons became dukes of Bedford, while their daughters were the Duchess of Bridgewater and the Countess of Essex.
Wriothesley died of smallpox at the age of 30, and rests in the Bedford Chapel of the parish Church of St. Michael, Chenies.