Cecil was born at Cavendish Square, London, the sixth child and third son of Robert Gascoyne-Cecil, 3rd Marquess of Salisbury, three times Prime Minister, and Georgina, daughter of Sir Edward Hall Alderson. He was the brother of James Gascoyne-Cecil, 4th Marquess of Salisbury, Lord William Cecil, Lord Edward Cecil and Lord Quickswood and the cousin of Arthur Balfour. He was educated at home until he was thirteen and then spent four years at Eton College. He claimed in his autobiography to have enjoyed his home education most. He studied law at University College, Oxford, where he became a well known debater. In 1887, he was admitted to the Bar (permitted to practise as a barrister). He was fond of saying that his marriage to Lady Eleanor Lambton in 1889 was the cleverest thing he had ever done.

From 1887 to 1906, Cecil practised civil law, including work in Chancery and parliamentary practice. On 15 June 1899, he was appointed as a Queen's Counsel (QC). He also collaborated in writing a book, entitled Principles of Commercial Law.

At the 1906 general election, Cecil was elected as a Conservative Member of Parliament representing Marylebone East. He did not contest the Marylebone seat in either of the general elections in 1910 as a result of the Tariff Reform controversy. Instead he unsuccessfully contested Blackburn in the January election and Wisbech in the December election. In 1911 he won a by-election in Hitchin, Hertfordshire, as an Independent Conservative and served as its MP until 1923.

Fifty years old at the outbreak of World War I and too old for military service, Cecil went to work for the Red Cross. Following the formation of the 1915 coalition government, he became Parliamentary Under-Secretary of State for Foreign Affairs on 30 May 1915. He served in this post until 10 January 1919, additionally serving in the cabinet as Minister of Blockade between 23 February 1916 and 18 July 1918. He was responsible for devising procedures to bring economic and commercial pressure against the enemy.

On 25 May 1923, Cecil returned to the cabinet as Lord Privy Seal, a position held by several members of his family. He did not stand again in the general election of December 1923 and, after the Conservatives lost their majority, he was raised to the peerage as Viscount Cecil of Chelwood, of East Grinstead in the County of Sussex, on 28 December 1923. He remained Lord Privy Seal until 22 February 1924, when Ramsey MacDonald's minority Labour cabinet took office.

The Conservatives returned to power at the October 1924 general election and Cecil became Chancellor of the Duchy of Lancaster. He was very concerned about the increasing social problems and public dangers associated with the growth in popularity of the motor car and in 1929 accepted the post of president of the newly formed Pedestrians Association who were to campaign successfully to introduce many measures of benefit to the pedestrian.

In September 1916, he circulated a memorandum making proposals for the avoidance of war, which he says was the "first document from which sprang British official advocacy of the League of Nations."

Cecil was an Esperantist, and, in 1921, he proposed that the League of Nations adopt Esperanto as solution to the language problem. From the inception of the League, after World War I, to its demise in 1946, Cecil's public life was almost totally devoted to the League. At the Paris Peace Conference, he was the British representative in charge of negotiations for a League of Nations; from 1920 until 1922, he represented the Dominion of South Africa in the League Assembly; in 1923 he made a five-week tour of the United States, explaining the League to American audiences. In the Conservative administrations of 1923 to 1924, and 1924 to 1927 he was the minister responsible, under the jurisdiction of the Foreign Secretary, for British activities in League affairs.

During a naval conference of 1927 in Geneva, negotiations broke down after the United States refused to agree to the British argument that Britain needed a minimum of seventy cruisers to adequately defend the British Empire and its trade and communications. The cutting of British cruisers to fifty from seventy was proposed by the Americans in return for concessions over the size of cruisers and the calibre of their guns. Cecil was part of the British delegation at Geneva and resigned from the cabinet because the British government let the conference break down rather than reduce the number of Britain's cruisers.

Although an official delegate to the League as late as 1932, Cecil worked independently to mobilise public opinion in support of the League. He was president of the British League of Nations Union from 1923 to 1945, and joint founder and president, with a French Jurist, of the International Peace Campaign, known in France as Rassemblement universel pour la paix. Among his publications during this period were The Way of Peace (1928), a collection of lectures on the League; A Great Experiment (1941), a personalised account of his relationship to the League of Nations; and All the Way (1949), a more complete autobiography.

In the spring of 1946, he participated in the final meetings of the League at Geneva, ending his speech with the sentence: "The League is dead; long live the United Nations!" He lived for thirteen more years, occasionally occupying his place in the House of Lords, and supporting international efforts for peace through his honorary life presidency of the United Nations Association.

Cecil's career brought him many honours. In addition to his peerage, he was created Companion of Honour in 1956, was elected chancellor of the University of Birmingham (1918 – 1944) and rector of the University of Aberdeen (1924 – 1927). He was given the Peace Award of the Woodrow Wilson Foundation in 1924. Most significantly, he was awarded the Nobel Peace Prize in 1937. He was presented with honorary degrees by the Universities of Edinburgh, Oxford, Cambridge, Manchester, Liverpool, St Andrews, Aberdeen, Princeton, Columbia, and Athens.

He died on 24 November 1958 at his home at Chelwood Gate, Danehill near Haywards Heath. He left no heirs and his Viscountcy became extinct.