She was trained at the ballet school of Teatro alla Scala in Milan and later with dancer/balletmaster Jules Perrot. At her 1836 debut in London Grisi performed with the accomplished danseur Jules Perrot. She next appeared in Paris at the Théâtre de la Renaissance (1840) and a year later, toured with Perrot to other parts of Europe. Through Perrot's contacts, the pair worked in Paris, London, Vienna, Munich, and Milan where she sang and danced.
Her greatest role however was that of Giselle. The world première of this two-act ballet was on June 28, 1841 at the Theatre de l'Academie Royale de Musique, Paris. The part of Albrecht was danced by Lucien Petipa, (the brother of the great Marius Petipa), with the part of Myrtha, Queen of the Wilis danced by Adele Dumilatre. It caused a sensation and inspired its reviewers to proclaim Giselle to be the greatest ballet of its time and a triumphant successor to the Romantic masterwork La Sylphide. As such, it immediately established Grisi as a star in her very first full-length ballet in Paris. Her salary grew from 5,000 francs to 12,000 in 1842 and 20,000 by 1844, with additional performance fees on top. Grisi's last performance in the west was in Paul Taglioni's Les Métamorphoses (aka Satanella, 1849).
In 1850, she joined Perrot in St. Petersburg, Russia, where he had been appointed balletmaster, and she danced Giselle at the Imperial Bolshoi Kamenny Theatre. The first Giselle in Russia had been danced by Fanny Elssler, and so the initial reaction to Grisi's interpretation of the role was not enthusiastic. However, over time the Russians appreciated her talents. She was Prima Ballerina of the St. Petersburg Imperial Theatres in St. Petersburg from 1850 to 1853, working not only with Perrot but also Joseph Mazilier who staged for her La Jolie Fille de Gand and Vert-Vert especially for her.
In 1854, with her daughter, she left Russia for Warsaw, where she intended to continue dancing, but she became pregnant by Prince Léon Radziwill who then persuaded her to retire from ballet at the height of her fame. Grisi gave birth to her second daughter, Léontine Grisi, and, at the age of 34, settled near Geneva to spend the next forty-six years of her life in peaceful retirement. She died in Saint-Jean, Geneva, Switzerland, on May 20, 1899, a month before her 80th birthday.