Marie Louise departed Vienna on March 13, probably expecting never to return. Upon arriving in France she was placed in the custody of Napoleon's sister, who had her put through a symbolic old ritual. Tradition dictated that a royal bride coming to France must keep nothing of her homeland, especially her clothes. Accordingly, Marie Louise was stripped of her gown, corset, stockings and chemise, leaving her completely naked. Napoleon's sister then made the nude teenager take a bath. She was then redressed in French bridal clothes. Marie Antoinette had been put through a similar ritual when she arrived in France in 1770. She met Napoleon for the first time on March 27 in Compiègne, remarking to him: "You are much better-looking than your portrait."

Archduchess Marie Louise of Austria (who was given the Latin baptismal name of Maria Ludovica Leopoldina Francisca Theresa Josepha Lucia) was born at the Hofburg Palace in Vienna on 12 December 1791 to Archduke Francis of Austria and his second wife, Maria Theresa of Naples and Sicily. She was named after her grandmother, Marie Louise, Holy Roman Empress. Her father became Holy Roman Emperor a year later as Francis II. Marie Louise was a great granddaughter of Empress Maria Theresa through both her parents, as they were first cousins. She was also a maternal granddaughter of Queen Maria Carolina of Naples, Marie Antoinette's favorite sister.

Marie Louise's formative years were during a period of conflict between France and her family. She was brought up to detest France and French ideas. Marie Louise was influenced by her grandmother Maria Carolina, who despised the French Revolution which ultimately caused the death of her sister, Marie Antoinette. Maria Carolina's Kingdom of Naples had also come into direct conflict with French forces led by Napoleon Bonaparte. The War of the Third Coalition brought Austria to the brink of ruin, which increased Marie Louise's resentment towards Napoleon. The Imperial family was forced to flee Vienna in 1805. Marie Louise took refuge in Hungary and later Galicia before returning to Vienna in 1806. Her father relinquished the title of Holy Roman Emperor but remained Emperor of Austria.

In 1807, when Marie Louise was 15, her mother died after suffering a miscarriage. Less than a year later, Emperor Francis married his first cousin Maria Ludovika Beatrix of Austria-Este, who was four years older than Marie Louise. Nonetheless, Maria Ludovika Beatrix took on a maternal role towards her stepdaughter. She was also bitter towards the French, who had deprived her father of the Duchy of Modena.

After escaping an assassination attempt in Vienna while negotiating the Treaty of Schönbrunn on 12 October 1809, Emperor Napoleon decided that he needed an heir to cement his relatively young Empire. He also sought the validation and legitimization of his Empire by marrying a member of one of the leading royal families of Europe. He began proceedings to divorce Joséphine de Beauharnais, who did not bear him a son, and began searching for a new Empress. His wish to marry Grand Duchess Anna Pavlovna of Russia, the youngest daughter of Tsar Paul I of Russia, caused alarm in Austria, who were afraid of being sandwiched between two great powers allied with each other. At the persuasion of Count Metternich, a marriage between Napoleon and Marie Louise was suggested by Emperor Francis to the Count of Narbonne but no official overture was made by the Austrians. Though officials in Paris and Austria were beginning to accept the possibility of the union, Marie Louise was kept uninformed of developments.

The civil wedding was held at the Saint Joseph's Church on 1 April 1810. The next day, Napoleon and Marie Louise made the journey to Paris in the coronation coach. The Imperial Guard cavalry led the procession, followed by the herald-at-arms and then the carriages. The Marshals of France rode on each side, near the doors of the carriages. The procession arrived at the Tuileries Palace, and the Imperial couple made their way to the Salon Carré chapel (in the Louvre) for the religious wedding ceremony. The ceremony was conducted by the Cardinal Grand Almoner of France. A Bridal March was composed for the occasion by Ferdinando Paer.

Marie Louise became pregnant by July 1810 and gave birth to a son on 20 March 1811. The boy, Napoléon François Joseph Charles Bonaparte, was given the title King of Rome, in accordance with the practice where the heir apparent to the Holy Roman Empire was called the King of the Romans. Napoleon was delighted that his wife survived the ordeal and said: "I had rather never have any more children than see her suffer so much again."

Marie Louise then travelled to Prague, where she spent a few weeks with the Austrian Imperial family, before returning to Saint Cloud on July 18. She kept in touch with Napoleon throughout the war. The invasion of Russia ended disastrously for France. More than half of the Grande Armée was destroyed by the Russian Winter and guerrilla attacks. After the failed Malet coup of October 1812, Napoleon hastened his return to France and reunited with his wife on the night of December 18.

In the summer of 1814, Emperor Francis sent Count Adam Albert von Neipperg to accompany Marie Louise to the spa town of Aix-les-Bains to prevent her from joining Napoleon on Elba. Neipperg was a confidant of Metternich and an enemy of Napoleon. Marie Louise fell in love with Neipperg. He became her chamberlain and her advocate at the Congress of Vienna. News of the relationship was not received well by the French and the Austrian public.

When Napoleon escaped in March 1815 and reinstated his rule, the Allies once again declared war. Marie Louise was asked by her stepmother to join in the processions to pray for the success of the Austrian armies but rejected the insulting invitation. She passed a message to Napoleon's private secretary, Claude François de Méneval, who was about to return to France: "I hope he will understand the misery of my position ... I shall never assent to a divorce, but I flatter myself that he will not oppose an amicable separation, and that he will not bear any ill feeling towards me ... This separation has become imperative; it will in no way affect the feelings of esteem and gratitude that I preserve." Napoleon was defeated for the last time at the Battle of Waterloo and was exiled to Saint Helena from October 1815. Napoleon made no further attempt to contact her personally.

Marie Louise departed for Parma on 7 March 1816, accompanied by Neipperg. She entered the duchy on April 18. She wrote to her father: "People welcomed me with such enthusiasm that I had tears in my eyes." She largely left the running of day-to-day affairs to Neipperg, who received instructions from Metternich. In December 1816, Marie Louise removed the incumbent prime minister and installed Neipperg.

Her first son, then known as "Franz," was given the title Duke of Reichstadt in 1818. Franz lived at the Austrian court, where he was shown great affection by his grandfather, but was constantly undermined by Austrian ministers and nationalists, who did their best to sideline him to become an irrelevance. There were fears that he might be smuggled over to France to regain the throne, as he could be easily disguised as a girl. Franz grew resentful at his Austrian relatives and his mother for their lack of support, and began identifying as Napoleon II and surrounding himself with French courtiers. The relationship with his mother broke down to such an extent that he once remarked "If Josephine had been my mother, my father would not have been buried at Saint Helena, and I should not be at Vienna. My mother is kind but weak; she was not the wife my father deserved; Josephine was." However, before anything could become of Napoleon II, he died at the age of 21 in Vienna in 1832, after suffering from tuberculosis.

Napoleon died on 5 May 1821. On August 8, Marie Louise married Neipperg morganatically. Neipperg died of heart problems on 22 February 1829, devastating Marie Louise. She was banned by Austria from mourning in public.

1831 saw the outbreak of the Carbonari-led uprisings in Italy. In Parma, protesters gathered in the streets to denounce the Austrian-appointed prime minister Josef von Werklein. Marie Louise did not know what to do and wanted to leave the city, but was prevented from doing so by the protesters, who saw her as someone who would Listen to their demands. She managed to leave Parma between 14 and 15 February, and a provisional government, led by Count Filippo Luigi Linati, was formed. At Piacenza, she wrote to her father, asking him to replace Werklein. Francis sent in Austrian troops, which crushed the rebellion. To avoid further turmoil, Marie Louise granted amnesty to the dissidents on September 29.

Metternich sent Charles-René de Bombelles to Marie Louise's household in 1833. Six months after his arrival, on 17 February 1834, she married him, again morganatically.

Marie Louise fell ill on 9 December 1847. Her condition worsened for the next few days. On December 17, she passed out after vomiting and never woke up again. She died in the evening. The cause of death was determined to be pleurisy.

Marie Louise was an obedient wife and settled in quickly in the French court. She developed a close friendship with her Première dame d'honneur, the Duchess of Montebello, while most of the daily affairs were handled by her Dame d'atour Jeanne Charlotte du Luçay. Napoleon initially remarked that he had "married a womb" to an aide, but their relationship soon grew. He "spared no pains" to please her and claimed at one point to prefer Marie Louise to his first wife Joséphine; while he had loved Joséphine, and though he claimed Joséphine remained his greatest friend even after their amicable divorce, he had not respected her, whereas with Marie Louise, there was "Never a lie, never a debt" — presumably a reference to Joséphine's rumoured extramarital affairs and reputation as a spendthrift. Marie Louise wrote to her father: "I assure you, dear papa, that people have done great injustice to the Emperor. The better one knows him, the better one appreciates and loves him." However, the marriage was not without tension; Napoleon sometimes remarked to aides that Marie Louise was too shy and timid, compared to the outgoing and passionate Josephine, with whom he remained in close contact, upsetting Marie Louise.