Wyndham was a member of Parliament (MP) from 1734 to 1750: for Bridgwater 1734-1741, Appleby 1741-1747, and Taunton 1747-1750. In October 1761 he was appointed Secretary of State for the Southern Department in succession to William Pitt. His term of office, during which he acted in concert with his brother-in-law, George Grenville, was mainly occupied with the declaration of war on Spain and with the negotiations for peace with France and Spain, the terms of which the earl seems to have disliked. He was also involved with the proceedings against John Wilkes. He died on 21 August1763. Horace Walpole perhaps rates Egremont's talents too low when he says he had neither knowledge of business, nor the smallest share of parliamentary abilities.