Edmund Sheffield was born in December 1611 to Sir John Sheffield (drowned in 1614), son of Edmund Sheffield, 1st Earl of Mulgrave, and Grizel Anderson, daughter of Sir Edmund Anderson, Chief Justice of the Common Pleas.
He sat in the House of Lords until its abolition, and was a member of the Council of State during the Commonwealth.
In 1658 he was nominated as a member of Cromwell's Upper House, but, like most of the other peers summoned, declined to serve.
Mulgrave married Elizabeth Cranfield, daughter of the Earl of Middlesex.
Their son, John, who succeeded to the earldom, was later created Marquess of Normanby and Duke of Buckingham and Normanby, and was Lord Privy Seal and Lord President of the Council during the reign of Queen Anne.