Prime Minister, Pelham was elected Member of Parliament for Seaford in 1717, and for Sussex in 1722. In 1721 he was appointed a Lord of the Treasury, as Secretary at War in 1724 and as Paymaster of the Forces in 1730. He was conspicuous in his support for Walpole and influential in policy.

Pelham became Prime Minister on the death of the Earl of Wilmington, gaining the posts of First Lord of the Treasury, Chancellor of the Exchequer and Leader of the House. However, Lord Carteret remained the more powerful figure until he was forced out of the ministry in 1744. Pelham worked closely with his brother, the Duke of Newcastle, and when the King, unhappy with their policies, made overtures to Lord Bath in 1746, both men resigned and the monarch was forced to invite them to resume office two days later, other politicians proving unable to form a government.

Pelham held office until his death, and was succeeded by his brother.

He was Prime Minister during the First and Second Carnatic Wars in India, and during the arrival in India of Robert Clive.