The second son of Sir Robert Walpole, he was educated at Eton (1718) and King's College, Cambridge (1725) and studied law at Lincoln's Inn (1723), where he was called to the bar in 1727.

Walpole first entered Parliament as Member for Lostwithiel in a by-election on 29 April 1730, following the death of Sir Edward Knatchbull earlier that month.

Walpole was sworn of the Privy Council of Ireland on 8 October that year and stood for Ballyshannon in the Irish House of Commons, a seat he held until 1760.

Walpole lived for a time at Frogmore House in Windsor, Berkshire which he bought in 1748 and sold in 1766.

He then bought a house in Windsor, which he gave to his daughter Laura Keppel in 1778, and spent his last years in Isleworth, where he died in 1784.