Eleanor - commonly called 'Nell' - Gwynne was born on 2nd February 1650, traditionally in the city of Hereford, although the Coal Yard off Drury Lane, London,  may have been her real birthplace. Her family was certainly of Welsh origin. Her father, Captain Thomas Gwynne, appears to have been a soldier ruined by the Civil War. Her mother, who lived with Nell for some time, drowned in a pond at Chelsea (Middlesex) in July 1679, apparently after becoming inebriated.

Nell Gwynne, who originally sold oranges in the precincts of the Drury Lane Theatre, became an actress at the age of only fifteen, through the influence of her first lover, the actor, Charles Hart, and also of Robert Duncan, a guards officer who had an interest in the theatre's management. Her first recorded appearance on the stage was in 1665, as Montezuma's daughter, Cydaria, in Dryden's Indian Emperor, a serious part to which she was not well. In the following year, however, she played Lady Wealthy in James Howard's comedy The English Monsieur. The diarist, Samuel Pepys, was apparently delighted by the performance from "pretty, witty Nell", but went further upon seeing her as Florimel in Dryden's Secret Love, or the Maiden Queen, : "so great a performance of a comical part was never, I believe, in the world before.....so done by Nell her merry part as cannot be better done in nature" (25th March 1667). Nell's success brought her other leading roles: Bellario, in Beaumont and Fletcher's Philaster; Flora, in Rhodes's Flora's Vagaries; Samira, in Sir Robert Howard's Surprisal. Nell Gwynne excelled in the delivery of the risqué, but fashionable, prologues and epilogues of the time, but her success as an actress was largely due to John Dryden, who wrote characters especially for her, having made a study of her airy and irresponsible personality. She remained a member of the Drury Lane company until 1669, playing continuously except for a short sabbatical in Epsom in the Summer of 1667, when she lived as the mistress of Charles Sackville, styled Lord Buckhurst (subsequently 6th Earl of Dorset).

It was as the mistress of King Charles II, from 1670 until his death, however, that Nell endeared herself to the public. Her popularity was only partly due to the antipathy inspired by her French Catholic rival, Louise de Keroualle, Duchess of Portsmouth. To a large extent it was the same personal qualities which appealed to the King that the poulace found agreeable. She was short, a minx rather than a beauty, with long reddish-brown hair. She was illiterate and, only with difficulty, scrawled an awkward EG at the end of letters written on her behalf. However, her candid recklessness, her generosity, her invariable good temper, her ready wit, her infectious high spirits and amazing indiscretions appealed irresistibly to a generation which welcomed in her the living antithesis of Puritanism. "A true child of the London streets," she never pretended to be more than she was, nor to interfere in matters outside the special sphere assigned her. She had no interest in influencing appointments or concerning herself with national or international politics.

Nell lived either in Pall Mall in Westminster or Church Street in Windsor, in order to be near the King while at his palaces. Her last appearance on the stage was in late 1670, as Almahide to Hart's Almanzor in The Conquest of Granada by Dryden. Its production had had to be postponed for some months while the theatre awaited her return after the birth of her first son by King Charles. The monarch then built for her, 'Burford House,' a fine mansion on the edge of the Home Park, 250 yards from the walls of Windsor Castle. Parts of it remain today incorporated into the Royal Mews. She never forgot her old friends though and, as far as is known, remained faithful to her Royal lover from the beginning of their intimacy until his death, and, after his death, to his memory.