In Vienna on 21 November 1891, she married Prince Frederick Augustus of Saxony who later became Crown Prince on the death of his childless Uncle, King Albert I and the accession of his father, King George in June 1902. They had seven children:
The two eldest sons, Friedrich August and Friedrich Christian, were born in the same year, 1893, but were not twins. Friedrich August was born in January, while Friedrich Christian was born in December.
Luise was very popular in Saxony. However, she did not follow etiquette at the court, which resulted in arguments with her father-in-law, King George of Saxony.
On 9 December 1902 Luise fled from Dresden due to her father-in-law threatening to have her interned in Sonnestein Mental Asylum for life. Her brother supported her in her wish to escape Saxony. She left Saxony without her children, but pregnant with Anna. For a while, she lived with her children's French tutor, André Giron, who was wrongly believed to be the father of her youngest daughter, Anna.
She was divorced from her husband on 11 February 1903 by the royal decree of her father-in-law. Emperor Franz Josef did not acknowledge the civil divorce.
On 25 September 1907, Luise married the Italian musician Enrico Toselli in London. They had one son, Carlo Emanuele Toselli (7 May 1908 – 1969), and were divorced five years later.
It was only after her second marriage that, Emperor Franz Josef, as head of the House of Habsburg, stripped her of her imperial titles and dignities. Her father created her Countess of Montignoso, as sovereign of the former Grand Duchy of Tuscany. After protracted negotiations, Anna was sent to Dresden to live with her siblings and be raised as a member of the Saxon royal house. Luise had tried to return to Dresden, but was prevented from seeing her children by her husband's ministers. She was allowed to see them on a private visit to a Saxon embassy. None of her children ever spoke out against their mother in their memoirs.
In 1911, Luise broke her silence and published a memoir blaming her disgrace on her late father-in-law and Saxon politicians, whom she claimed feared that when she became queen, she would use her influence to dismiss them from office. Throughout the book, she claimed that her popularity exceeded that of her father-in-law, King Georg of Saxony, and her husband, the future king. There is strong evidence to support this. Luise implied that her popularity had alienated her from the royal family and politicians. Luise was indeed popular with the Saxon people. She ascribed her popularity to her insistence on ignoring the etiquette of the Saxon court and, perhaps to cast herself as a victim, compared herself to her Habsburg relative, Marie Antoinette, who disliked court rituals at Versailles and, like Luise, had avoided the noble courtiers who depended on those rituals to affirm their places at court. Her sister-in-law, Mathilda did a great deal to harm her.
After the Habsburg monarchy collapsed in 1918, Luise called herself "Comtesse d'Ysette", a title with even less legitimacy than the one her father had given her. Her former husband, the ex-King of Saxony, never remarried, as he believed in the eyes of the Roman Catholic Church that he was still married to Luise.
She died in Brussels and her urn is in the Erdlinge Church in Sigmaringen. A number of her children are buried nearby including her son Prince Ernst Heinrich.