Although Talma's father, a dentist, wanted his son to become a dentist as well, young Talma spent his time instead in amateur theatricals and made his professional debut at the Comédie-Française on Nov. 21, 1787, as Seide in Voltaire's Mahomet. Influenced by his friend the painter David, he became one of the early advocates of historical costuming when he appeared in a Roman toga and headdress in the small role of Proculus in Voltaire's Brutus.

Until Nov. 4, 1789, Talma had taken only minor roles; on that day he took over the title role in Marie-Joseph-Blaise de Chenier's anti-monarchical Charles IX after it had been turned down by other actors, who feared political difficulties. As expected, the play caused demonstrations in the theatre and aroused such dissension in the company that the pro-republican Talma established a rival troupe known as the Théâtre de la République. There he developed realism in staging and costuming while producing classical French drama and translations of Shakespeare. In acting he insisted upon a realistic rather than a declamatory style and made speaking pauses follow the sense of speeches rather than their metre.

In 1799, when the two companies were reunited at Talma's theatre as the Comédie-Française, he emerged as the supreme tragedian of the era, winning the admiration and patronage of Napoleon. Talma wrote “Réflexions sur Lekain et l'art théâtral” as a preface to the memoirs of the French actor Lekain. His last appearance was in Delaville's Charles VI on June 3, 1826.