He was born to Walter Edward Guinness (created 1st Baron Moyne in 1934), son of the 1st Earl of Iveagh, and Lady Evelyn Stuart Erskine, daughter of the 14th Earl of Buchan. He attended Heatherdown, Eton College, and Christ Church, Oxford, and was called to the Bar in 1931.
As an heir to the Guinness brewing fortune and a handsome, charming young man, Bryan was an eligible bachelor. In 1929, he married the Hon. Diana Mitford, one of the infamous Mitford sisters, and had two sons with her. The couple became leaders of the London artistic and social scene and were dedicatees of Evelyn Waugh's first novel Vile Bodies. However, they divorced in 1933, after Diana deserted him for British fascist leader Sir Oswald Mosley. Bryan remarried happily in 1936 to Elisabeth Nelson, with whom he would have nine children.
In 1944, while serving his country as a liaison officer, Bryan succeeded to the barony when his father, posted abroad as a Minister Resident in the Middle East, was assassinated in Israel. After the war, he served on the board of the Guinness corporation, as well as various trusts and artistic committees in Ireland. He wrote a number of critically applauded novels, memoirs, books of poetry, and plays.
Bryan died in 1992 at Biddesden, his home in Hampshire, and was succeeded by his eldest son Jonathan.