Lloyd was educated at Fettes College and Magdalene College, Cambridge, where he was President of the Cambridge Union, and was a Liberal Parliamentary candidate in the 1929 General Election. He served as a councillor on Hoylake Urban District Council 1932-40. During the Second World War he reached the rank of brigadier and was Deputy Chief of Staff of the British Second Army. He was elected to the House of Commons to represent Wirral in the 1945 UK general election. Originally a Liberal, he became a member of the "Young Turks" faction of the Conservative Party. When the Conservatives returned to power under Churchill in 1951, Lloyd served under Foreign Secretary Anthony Eden as Minister of State for Foreign Affairs from 1951 to 1954. He then served as Minister of Supply (1954-1955) and Minister of Defence (1955), before becoming himself Foreign Secretary in the same year. His tenure saw the Suez Crisis, which led to the fall of the Eden government, but he continued to serve as Foreign Secretary under Harold Macmillan until 1960, then becoming Chancellor of the Exchequer (1960-1962).
Unable to cope with Britain's economic problems in the early 1960s, he was sacked from the government during the "Night of the Long Knives" reshuffle, and returned to the backbenches, but was called back to the government in 1963 by Alec Douglas-Home, who made him Lord Privy Seal and Leader of the House of Commons until the Conservative defeat in the General Election of 1964. In 1971, after the Conservatives had returned to power, Lloyd became Speaker. In a break with convention, both the Labour and Liberal Parties contested his seat in the 1974 general elections, but he retained it and continued to hold the position of speaker until 1976, when he was raised to the peerage as Baron Selwyn-Lloyd, of Wirral in the County of Merseyside. He died two years later.
A biography of Selwyn-Lloyd by D. R. Thorpe was published in 1989.