In 1880, he married Sibyl Marcia Graham—daughter of Sir Frederick Graham, 3rd Baronet of Netherby—who died in 1887, leaving him with three daughters and one a son:
In 1895 he was created Earl of Crewe, after his maternal grandfather, the 2nd Baron Crewe, left him as heir. He was created Marquess of Crewe and Earl of Madeley in 1911, but all his titles ended with his death in 1945 because of lack of a male heir.
Crewe-Milnes' second marriage (1899) was to Margaret, daughter of the 5th Earl of Rosebery. They had a son, also Richard, born in 1911; however, he died in 1922. A daughter, Lady Mary Evelyn Hungerford Crewe-Milnes, survived and was the first wife of the 9th Duke of Roxburghe (father of the present Duke); they were divorced in 1953 without issue.
He inherited his father's literary tastes, and published Stray Verses in 1890, besides other miscellaneous literary work. He also wrote a biography, Lord Rosebery, published in 1931.
From 1905 to 1908 he was Lord President of the Council in the Liberal government; in 1908, in Asquith's cabinet, he became Secretary of State for the Colonies (1910–15) and Liberal leader in the House of Lords. In this latter role, he played a key part in bringing the Parliament Act of 1911 (depriving the Lords of its veto) to the statute book. His colonial responsibilities included terms as Secretary of State for India (1910–11 and 1911–15).
He served as Lord President of the Council again in 1915–16.
He maintained a leading role in the education sector, serving as Chaiman of the Governing Body of Imperial College London (1907–22), President of the Board of Education (1916) and Chancellor of Sheffield University. He was also chairman of London County Council in 1917.
He was later Ambassador to France (1922–28), and Secretary of State for War in 1931. As Ambassador to France he launched a fund for the creation of a British Institute in Paris which has since developed into the University of London Institute in Paris (ULIP).
His father-in-law, Lord Rosebery, had been Liberal Leader six years before he himself became Leader in the House of Lords of that party. Rosebery thought Crewe a reliable politician but a poor speaker. When it was announced to him that his daughter, the Marchioness of Crewe, was in labour, Rosebery quipped, "I hope that her delivery is not as slow as Crewe's".