The sitter, generally known as Horace, was born on 8 December 1678, the fifth (second surviving) son of Robert Walpole (1650-1700) and his wife, Mary (1654/5-1711), the daughter and heir of Sir Jeffrey Burwell of Rougham, Suffolk. His elder brother was Sir Robert Walpole, first earl of Orford. Horace was educated at Eton and King's College, Cambridge, and first entered parliament in 1702, serving in the House of Commons for a total of nearly fifty-four years. His political career was largely owed to his brother's term as Prime Minister (1721-42). In 1709 he was sent to the Netherlands (serving first as secretary to the embassy 1709-11, and subsequently as British Minister at the Hague 1715-16). In 1723 he travelled to Paris, where he became ambassador-extraordinary and plenipotentiary, a post he held until 1730. Walpole had an admirable understanding of international relations, and one of his greatest achievements was the engineering, together with Stephen Poyntz, of the treaty of mutual defence between Britain, France, and Spain, which was signed in Seville on 9 November 1729.
In 1720, Walpole married Mary Magdalen (1694/5-1783), daughter of Peter Lombard, of Burnham Thorpe, Norfolk, and the couple had four sons and three daughters. Their eldest son Horatio (1723-1809) succeeded his father as second Baron Walpole upon the latter's death on 5 February 1757, further inheriting the estate of his cousin Horace, fourth earl of Orford.