In 1771 Louise's younger sister (also a canoness at St. Waudru) married the Marquess of Jamaica, only son of the 3rd Duke of Berwick (great-grandson of King James II of England and VII of Scotland). The Duke of Berwick's uncle, the duc de Fitz-James, began negotiations with Louise's mother for a marriage between Louise and Charles Edward Stuart, the Jacobite claimant to the English and Scottish thrones. Although King Louis XV of France recognised the succession of the House of Hanover, he also hoped that the legitimate Stuart line would not die out and would be an ongoing threat to the Hanoverians.
The negotiations were delicate since Louise's family had no money of its own and relied totally on the goodwill of the Empress Maria Theresa (who was allied to the Hanoverians). On 28 March 1772 Louise was married by proxy to Charles Edward at Paris. The couple met for the first time on 14 April 1772 when they renewed their marriage vows in person in the town of Macerata, Italy. Louise was henceforward recognised by Jacobites as Queen Louise of England, Scotland, France, and Ireland.
Charles and Louise spent the first two years of their married life in Rome. In spite of the difference in their ages (he was 52, she was 20), the couple were at first happy together. But there were several shadows on the relationship. There was no sign of Louise conceiving a child. Charles had been encouraged in the belief that, if he married, the pope would recognise him as King of England and Scotland, and France might provide funds for another Jacobite rising. Louise had virtually been promised that she would be treated as a queen. Instead Charles found his hopes both of a son and of diplomatic recognition disappointed, while Louise found herself married to an old prince with no prospects.
In 1774 Charles and Louise moved to Florence. It was there that they began to use the title "Count and Countess of Albany". In 1776 the Italian poet Count Vittorio Alfieri was presented at their palace; he became a frequent visitor. In Rome Louise had had several young men pay court to her, but these relationships had probably not been adulterous. But sometime in 1778 Louise and Alfieri became lovers.
Meanwhile Louise's husband Charles had become a drunkard again as he had been a number of years before. In December 1780 Louise left Charles and took refuge in a convent. She claimed, and it is widely believed to be true, that Charles had become physically abusive to her.
In April 1784 Charles was induced by King Gustav III of Sweden to grant Louise a decree of separation. The couple did not divorce (since no such legal procedure existed in the Papal States), but Louise was thereby permitted to live separately from her husband.
On the last day of January 1788, Louise's husband Charles died. This resulted in a substantial improvement in her financial situation thanks to a previously agreed pension from the King of France.