When she was seventeen, she married George Villiers, 4th Earl of Jersey, son and heir of William Villiers, 3rd Earl of Jersey and his wife Lady Anne Egerton. Her husband was nearly twenty years older and was Master of Horse to the Prince of Wales and a Lord of the Bedchamber. The reason for the marriage of Lord Jersey to the daughter of a disreputable Irish bishop has not been explained in contemporary accounts.
Having encouraged the Prince of Wales to marry his first cousin, Princess Caroline of Brunswick, Lady Jersey nevertheless set out to make Caroline's life difficult. However, the now Queen consort (Caroline) had very little regard for George IV, nor did he care for her deeply, and after the birth of their child together, Caroline lived abroad for most of her 25 year marriage to him, taking other lovers, and therefore leaving a void Frances could fill.
Since she enjoyed the favour of Queen Charlotte, even the displeasure of the king was not enough to threaten Lady Jersey's position, and she continued to run the prince's life and household for some time. Eventually, though, he replaced her and she would slowly decline from any active involvement with the royal court.
According to Archaelogia Cantiana,
"The home of the Bishop's daughter Frances, Lady Jersey, a favourite of George IV, became a society gambling rendezvous, at which the reputations of her cousins were in no way enhanced.
She had remained married to George Villiers throughout. In about 1803, her previously undisputed place as senior royal mistress was taken by Lady Hertford. In 1805 her husband died, after a long marriage which had produced ten children.
Lady Jersey died at Cheltenham and was buried at Middleton Stoney.