Shortly after her introduction to society at age 18 she met, and became secretly engaged to Bryan Walter Guinness, an Irish aristocrat, writer and brewing heir who would inherit the barony of Moyne. Her parents were initially opposed to the match but in time were convinced. The marriage on January 30, 1929, was the marriage of the year.
The couple had an income of £20,000 a year, an estate in Hampshire and houses in London and Dublin. They were well known for hosting glittering society events involving writers such as Evelyn Waugh, Lytton Strachey, Dora Carrington and John Betjeman, or politicians such as Winston Churchill. Waugh dedicated the novel Vile Bodies, a satire of the Roaring Twenties, to the couple. They had two sons, Jonathan and Desmond.
In 1932 she became the mistress of British Fascist leader Sir Oswald Mosley; he was then married to Lady Cynthia Curzon, a daughter of Lord Curzon, former Viceroy of India and his first wife, American mercantile heiress Mary Victoria Leiter. Diana soon left her husband but Sir Oswald would not leave his wife.
Sir Oswald's wife died of peritonitis in May of 1933 and the grief stricken Oswald began an affair with another woman. Diana went to Germany with her then 19 year old sister Unity. While there they attended the first Nuremberg rally. They returned again for the second rally the next year during which Unity struck up a friendship with Hitler. She introduced Diana to him in March 1935. They were his guests at the 1935 rally and in 1936 Hitler provided a Mercedes to chaufeur Diana to the Berlin Olympic games.
She continued to be Sir Oswald's public mistress despite his contiued affairs with other women. On October 6, 1936, in the Berlin drawing room of Joseph Goebbels, she became Sir Oswald Mosley's second wife. Other than the witnesses, the only guests were Goebbels and Hitler. Hitler presented the couple with a silver framed picture of himself. The marriage was kept secret until the birth of their first child Alexander in 1938.
In August 1939, Hitler told Diana over lunch that war was inevitable. Under Defence Regulation 18B she and her husband were interned throughout much of World War II for their Fascist sympathies. They were initially held separately but, after personal intervention by Churchill, Sir Oswald became the only male prisoner held at London's Holloway Prison. After two years imprisonment, in November 1943, they were both released on grounds of Sir Oswald's health. They were placed under house arrest until the end of the war.
Lady Mosley's prison time failed to disturb her manifestly blinkered approach to life, remarking in her later years that she never grew fraises des bois that tasted as good as those she cultivated in the prison garden. She also survived her time there by basking in her own imperishable self-regard: Though prison was not something she would have chosen, she said, "It was still lovely to wake up in the morning and feel that one was lovely one."
After the war ended she and her husband moved to Ireland for a few years and then settled in France where they lived in a large house at Orsay near Paris called Temple de la Gloire. They were neighbours, and soon became close friends of, the Duke and Duchess of Windsor. They were well known for entertaining but were barred from all functions at the British Embassy.
While in France Diana edited the right-wing magazine The European to which she also contributed.
After her marriage she was a lifelong supporter of the British Union of Fascists and its postwar successor The Union Movement, to which she made financial contributions until the 1994 death of its organiser Jeffrey Hamm. She often attended its annual dinners.
MI5 documents released in 2002 gave a harsh view of Lady Mosley and her politicial leanings. "Diana Mosley, wife of Sir Oswald Mosley, is reported on the best authority, that of her family and intimate circle, to be a public danger at the present time. Is said to be far cleverer and more dangerous than her husband and will stick at nothing to achieve her ambitions. She is wildly ambitious." Lady Mosley, however, continued to admire Hitler and the tenets of Nazism throughout her life but was open in addressing the Führer's faults. "I'm sure he was to blame for the extermination of the Jews," she told British journalist Andrew Roberts. "He was to blame for everything, and I say that as someone who approved of him."
Mitford died in Paris in August 2003 from complications related to a stroke she had suffered a week earlier.
She had four children, among whom are the Irish preservationist Desmond Guinness, the writer Jonathan Guinness (3rd Lord Moyne), and the president of the FIA, the governing body of world motorsport, Max Mosley. Her stepson Nicholas Mosley is a well-known British novelist.
She wrote two books of memoirs, A Life of Contrasts, 1977, and Loved Ones, 1985, as well as a biography of the Duchess of Windsor.