Guest was born at Uffington House in Uffington, Lincolnshire, the daughter of Albemarle Bertie, 9th Earl of Lindsey and his second wife Charlotte Susanna Elizabeth Layard. Her father died when she was six, and her mother remarried to Reverend Peter Pegus, whom Charlotte disliked. She showed a great talent for study and taught herself Arabic, Hebrew, and Persian.

After what may have been a brief flirtation with the future Prime Minister Benjamin Disraeli, she escaped her unhappy home life through marriage in 1833, which was, however, not a conventional one for her age. Her husband, John Josiah Guest, was an industrialist in Wales, the owner of the Dowlais Iron Company and rather older than her; he was 49 while she was 21. They moved to Dowlais in Merthyr Tydfil after he was elected Member of Parliament for the constituency in 1832. Charlotte was very happy in her marriage, which produced ten children. She took an enthusiastic interest in her husband's philanthropic activities on behalf of the local community and also became involved in the business of the iron works, translating technical documents into French. John Guest eventually obtained a baronetcy in 1838.

The decline of her husband's health meant that Charlotte spent more time administering the business and took over completely following his death in 1852. She stood up to both her workers and other foundry owners until she relinquished her position to G. T. Clark in 1855 upon her marriage to Charles Schreiber. Schreiber was a classical scholar and a Member of Parliament for Cheltenham and later Poole. They left Wales and spent many years travelling in Europe collecting ceramics which she bequeathed to the Victoria and Albert Museum. She also collected fans, board games and playing cards, which she donated to the British Museum.

Guest's eldest son Ivor eventually became First Baron Wimborne and married Lady Cornelia Spencer-Churchill, eldest daughter of the Seventh Duke of Marlborough and thus aunt to Winston Churchill. They were parents of the First Viscount Wimborne. Among her other descendants are the American Guests (the late socialite C. Z. Guest was wife of one of these), the Earls of Bessborough, the Viscounts Chelmsford, and others.

During her time in Wales, Guest learned Welsh and associated with literary scholars, including Thomas Price, Villemarqué, Judge Bosanquet, and Gwallter Mechain, who encouraged her in her work. She translated several medieval songs and poems, and eventually the Mabinogion, which was an immediate success. The name Mabinogion for these stories begins with Guest;the word Mabinogi technically applies to only the first four tales, known as the Four Branches of the Mabinogi. One manuscript contains the word mabynnogyon, which she took for a plural and applied to the collection as a whole.

The tales of the Mabinogion had been summarized in William Owen Pughe's Myvyrian Archaiology of Wales, and Pughe had completed a translation of the tales which was left unpublished at his death in 1835. Guest did not rely on Pughe's translations, though she did use a Welsh dictionary Pughe had completed in 1803. Her Mabinogion became the first translation of the material to be published. It was printed in several volumes between 1838 and 1849, with the first volumes dedicated to the Arthurian material; volume I contained the Welsh Romances Owain, Peredur, and Geraint and Enid, while volume two contained Culhwch ac Olwen and The Dream of Rhonabwy. Geraint and Enid served as the basis for Alfred, Lord Tennyson's two poems about Geraint in the Idylls of the King.

Lady Charlotte Guest was a "foreigner" (non-Welsh person) who helped revive Welsh culture. She is remembered, along with her near-contemporary Lady Llanover, as a great patron of the arts in Wales. A public house, built as part of the regeneration of Dowlais in the 1980s, was named the Lady Charlotte in her honour.

• March, Katherine. "Lady Charlotte (Elizabeth) Guest". From The Camelot Project at the University of Rochester. [1] Retrieved 3 April 2007.
• Schreiber, Lady Charlotte Guest. Biography from British Authors of the 19th Century; H. W. Wilson Company. 1936.

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