In his Histoire de ma vie (vol. 3, chap. 11), Giacomo Casanova relates that he found her "a pretty, ragged, dirty, little creature" of thirteen years in the house of her actress sister. Struck by her beauty when seeing her naked, however, he had a nude portrait of her painted, with the inscription "O-Morphi" (punning her name with Modern Greek ὄμορφη, "beautiful"), a copy of which found its way to the King, who took her as one of his mistresses. (This portrait is apparently not to be identified with the memorable and provocative portrait by François Boucher, though Casanova's description indicates that the poses were similar.)
She quickly became a favourite, and, after a miscarriage in 1753 (who apparently deeply affected the King), she gave birth Louis XV's illegitimate daughter, Agathe Louise de Saint-Antoine, born in Paris on 20 May 1754 and baptized that same day at Saint-Paul.
After serving as a mistress to the King for just over two years, O'Murphy made a mistake that was common for many courtesans, that of trying to replace the official mistress. Around 1754, she unwisely tried to unseat the longtime royal favorite, Madame de Pompadour. This ill-judged move quickly resulted in O'Murphy's downfall at court; a marriage was arranged to Jacques Pelet de Beaufranchet, seigneur d'Ayat on 27 November 1755.
Two years later, on 19 February 1759 at Riom, O'Murphy married again to François Nicolas Le Normant, comte de Flaghac, a widower with three children. From this union, O'Murphy gave birth a daughter, Marguerite Victoire (born 5 January 1768 - died 1814), who, according to one theory, could be another illegitimate daughter of Louis XV.