Sand's reputation came into question when she began sporting men's clothing in public — which she justified by the clothes being far sturdier and less expensive than the typical dress of a noblewoman at the time. In addition to being comfortable, Sand's male dress enabled her to circulate more freely in Paris than most of her female contemporaries, and gave her increased access to venues from which women were often barred — even women of her social standing. Also scandalous was Sand's smoking tobacco in public; neither peerage nor gentry had yet sanctioned the free indulgence of women in such a habit, especially in public (though Franz Liszt's paramour Marie D'Agoult affected this as well, smoking large cigars). These and other behaviors were exceptional for a woman of the early and mid-19th century, when social codes — especially in the upper classes — were of the utmost importance.
As a consequence of many unorthodox aspects of her lifestyle, Sand was obliged to relinquish some of the privileges appertaining to a baroness — though, interestingly, the mores of the period did permit upper-class wives to live physically separated from their husbands, without losing face, provided the estranged couple exhibited no blatant irregularity to the outside world.

Poet Charles Baudelaire was a contemporary critic of George Sand: "She is stupid, heavy and garrulous. Her ideas on morals have the same depth of judgment and delicacy of feeling as those of janitresses and kept women.... The fact that there are men who could become enamoured of this slut is indeed a proof of the abasement of the men of this generation."

Sand conducted affairs of varying duration with Jules Sandeau (1831), Prosper Mérimée, Alfred de Musset (summer 1833 – March 1835), Louis-Chrystosome Michel, Pierre-François Bocage, Félicien Mallefille and Frédéric Chopin (1837–47). Later in life, she corresponded with Gustave Flaubert. Despite their obvious differences in temperament and aesthetic preference, they eventually became close friends. She was engaged in an intimate friendship with actress Marie Dorval, which led to widespread but unconfirmed rumors of a lesbian affair. Letters written by Sand to Dorval mentioned things like "wanting you either in your dressing room or in your bed."

In Majorca one can still visit the (then abandoned) Carthusian monastery of Valldemossa, where she spent the winter of 1838–39 with Chopin and her children. This trip to Majorca was described by her in Un Hiver à Majorque (A Winter in Majorca), published in 1855. Chopin was already ill with incipient tuberculosis at the beginning of their relationship, and spending a winter in Majorca - where Sand and Chopin did not realize that winter was a time of rain and cold, and where they could not get proper lodgings - exacerbated his symptoms. They split two years before his death, for a culmination of reasons. Sand's insecurities at forty probably contributed to her boredom and sexual poverty with Chopin. In Lucrezia Floriani, a novel, Sand used Chopin as a model for a sickly Eastern European prince named Karol. He's cared for by a middle-aged actress past her prime, Lucrezia, who suffers a great deal by caring for Karol. Though Sand claimed not to have made a cartoon out of Chopin, the book's publication and widespread readership may have exacerbated their apathy to each other. However, the tipping point in their relationship involved her daughter, Solange. Chopin continued being cordial with her after she and her husband, Auguste Clesinger, had a vicious falling out with Sand over money. Sand took Chopin's lending a hand to Solange as outright treachery, and confirmation that Chopin had always "loved" Solange. Sand's son, Maurice, also disliked Chopin and wanted to establish himself more as the man of the estate. Chopin was never asked back to Nohant. In 1848, he returned to Paris from a tour of the UK and died at the Place Vendôme. Penniless, his friends paid for his stay there, and his funeral at the Madeleine. The event, with over 3,000 people attending including Delacroix, Liszt, Victor Hugo and other, did not see George Sand attend.

A liaison with the writer Jules Sandeau heralded her literary debut. They published a few stories in collaboration, signing them "Jules Sand." She consequently adopted, for her first independent novel, Indiana (1832), the pen name that made her famous – George Sand. Her first published novel, Rose et Blanche (1831), was written in collaboration with Jules Sandeau. Drawing from her childhood experiences of the countryside, she wrote the rural novels La Mare au Diable (1846), François le Champi (1847–1848), La Petite Fadette (1849), and Les Beaux Messieurs Bois-Doré (1857). A Winter in Majorca described the period that she and Chopin spent on that island in 1838-9. Her other novels include Indiana (1832), Lélia (1833), Mauprat (1837), Le Compagnon du Tour de France (1840), Consuelo (1842–1843), and Le Meunier d'Angibault (1845). Further theatre pieces and autobiographical pieces include Histoire de ma vie (1855), Elle et Lui (1859) (about her affair with Musset), Journal Intime (posthumously published in 1926), and Correspondence. Sand often performed her theatrical works in her small private theatre at the Nohant estate. In addition, Sand authored literary criticism and political texts. She wrote many essays and published works establishing her socialist position. Because of her early life, she sided with the poor and working class. When the 1848 Revolution began, women had no rights and Sand believed these were necessary for progress. Around this time Sand started her own newspaper which was published in a workers' co-operative. This allowed her to publish more political essays. She wrote "I cannot believe in any republic that starts a revolution in killing its own proletariat." Her most widely used quote is "There is only one happiness in life, to love and be loved."

She was known well in far reaches of the world, and her social practices, her writings and her beliefs prompted much commentary, often by other luminaries in the world of arts and letters.

George Sand died at Nohant, near Châteauroux, in France's Indre département on 8 June 1876, at the age of 71 and was buried in the grounds of her home there. In 2004, controversial plans were suggested to move her remains to the Panthéon in Paris.