Hortense Mancini wurde im Jahr 1661 mit Armand-Charles de La Porte, dem Marquis de La Meilleraye und Herzog von Mazarin und Herzog von Mayenne, verheiratet, dem sie vier Kinder, drei Töchter und einen Sohn, schenkte. Es war eine sehr unglückliche Ehe, der Hortense zu entfliehen versuchte, indem sie sich im Jahr 1666 zuerst in ein Kloster und im Jahr 1668 schließlich nach Italien begab. Dort fand sie letztendlich Asyl beim Herzog Karl Emanuel II. (1634-1675), mit dem sie einst im Jahr 1658 verheiratet werden sollte. Nach dessen Tod begab sie sich nach England zum englisch-schottischen König Karl II. (1630-1685), mit dem man sie Jahr 1661 vermählen wollte. "There [in England] at her house next to Saint James's Palace, she began to receive all the most illustrious people in literature, philosophy, and politics; her faithful friend from then until her death was another French expatriate, the writer and courtier Saint-Evremond, who was thirty years her senior. ... Meanwhile, the Duc Mazarin continued his efforts to force her back to him; extraordinarily litigious throughout his life - he was party to hundreds of lawsuits - he made one final legal sally against his wife in 1689 ... The Duc Mazarin asked the court to deprive Hortense of her dowry and order her either to return unconditionally to him or be confined to a convent. The court ruled in his favor and ordered Hortense to return to France, but her lawyer argued that English law prevented her from leaving the country until her very considerable debts had been paid; the Duc Mazarin refused to recognize those debts, saying that a wife had no legal authority to contract them without her husband's permission ... In the end, Hortense remained in England until her death in 1699 ..." (in: Hortense Mancini and Marie Mancini: Memoirs, Edited and Translated by Sarah Nelson, id., pp. 5-6).
"Hortense ... was being kept away from court and dragged all over France by her intensely jealous and fanatically religious husband, who obliged her to come with him as he traveled from one to another of the many governorships he had inherited from Cardinal Mazarin ... that she was finally pushed to lodge a public complaint against her husband when it became clear to her that he was dissipating the inheritance that was to go to her son. In her memoir, Hortense recounts her various attempts to leave her husband and to obtain a formal separation through the parlament of Paris or from the king, beginning some time after her son's birth in 1666. By 1668, matters had come to such a pass that Hortense fled Paris in the dark of night, her maid [Nanon] and she dressed in men's clothing; they traveled to Italy and were received by Marie [Maria Mancini] and her husband. There the sisters were joined by their brother Philippe [(1641-1707)], duc de Nevers, with whom they amused themselves in grand style, hosting elaborate balls and constantly planning their next journey to Venice for the carnival season. ... Philippe and Hortense made a journey back to Paris in 1670-71 ... she to pursue her efforts toward legal separation and to obtain a pension from her husband which would allow her to live comfortably in Italy. She obtained neither, but she did get the king's blessing and a promise of a small ... pension from the royal coffers. She returned to Rome, where relations between Marie and her husband were ever more strained; by the spring of 1672, the two sisters had determined to flee together and to return to France in the hope of winning Louis XIV's protection and being allowed to live independently from their husbands." (in: Hortense Mancini and Marie Mancini: Memoirs, Edited and Translated by Sarah Nelson, id., pp. 4-5).
Hortense nennt in ihrer Biografie selbst den Grund, warum sie ihren Gatten im Jahr 1666 für immer verließ: "... for I do not believe that even the strictest rules of Christian charity require me to presume that the pious men by whom Monsieur Mazarin [ihr Gatte] has been governed are among the genuine believers, after they had led him to squander so many millions. And this is the fatal point which has pushed my patience to its limit, and which is the true source of all my misfortunes. If Monsieur Mazarin had been content to overwhelm me with sadness and grief, to expose my health and my life to his most unreasonable whims, and in short to make me spend my best days in unparalleled servitude, then since heaven had given him to me as master, I would merely have moaned and complained of him to my friends. But when I saw that because of his unbelievable extravagance, my son [Paul-Jules (1666-1731), Duc Mazarin und Herzog de La Meilleraye], who would have become the richest gentleman in France, ran the risk of winding up the poorest, I had to give in to the force of blood ties, and motherly love won out over all the moderation that I had intended to observe. Every day I saw immense sums of money, priceless furniture, offices, governorships, and all the rich remains of my uncle's fortune disappear, the fruit of his labors and the reward of his services. I saw more than three millions' worth of it sold before I made any public protest; and there was almost nothing of value left to me but my jewels when Monsieur Mazarin took it into his head to seize them from me. He took advantage of his opportunity to lay hold of them one evening when I came home very late from the city. ... [die Situation innerhalb ihrer Ehe wurde unerträglich] ... Monsieur Mazarin, who, as you will see, had taken steps to keep me from going out when I wished and to make a prison of my palace, threw himself in front of me and pushed me very roughly, in order to block my way; but my grief and vexation gave me extraordinary strength, and I broke through even though he was strong, too. And though he screamed like mad out the window to close all the doors and especially the gate of the courtyard, nobody, when they saw me all in tears, dared to obey him. I went around to the other side through the street, which was very crowded, in this sad state, alone, on foot, and in the middle of the day, to reach my usual refuge [bei ihrem Bruder Philippe]. [Sie wurde gezwungen, zu ihrem Gatten zurückzukehren.] ... Monsieur Mazarin gave me the choice staying at the hôtel de Conti or at the abbey of Chelles, the two places in the world which he knew I most hated ... the arguments against the hôtel de Conti were so strong that Chelles was preferred. ... In the meantime [nach vielen Monaten] I obtained a ruling in my favour in the third chamber of the Enquêtes. ... It was declared that I would go to live at the Palais Mazarin, and Monsieur Mazarin at the Arsenal, that he would give me a pension of twenty thousand francs; and ... that he would produce the documents with which I intended to prove that he had wasted my son's fortune. ... Monsieur Mazarin had brought our case before the Grand'Chambre, to have it reexamined ... We signed a document ..., which declared that Monsieur Mazarin would come back to live at the Palais Mazarin, but that I would be free to choose all my servants as I wished, with the exception of an equerry whom I would be given by Monsieur Colbert; that we would each stay in our own apartments, that I would not be obliged to follow him on any journey; and that in the matter of the separation of property which I requested, Messieurs les Ministres would be the arbitrators, and we would inviolably observe and obey what they said." (in: Hortense Mancini and Marie Mancini: Memoirs, Edited and Translated by Sarah Nelson, id., pp. 44/47/49/52-53). Nachdem ihr Gatte das Gericht zu seinen Gunsten erneut beeinflussen konnte und Hortense damit zu rechnen hatte, mit ihrem Gatten wieder zusammenleben zu müssen, floh sie schließlich nach Italien.