At the death of her brother King Ladislaus in 1414 Joanna II succeeded to the Neapolitan crown.
Her life had always been very dissolute, and although widowed at 41, few years later, being forty-five, she chose as her lover Pandolfo Alopo, a youth of twenty-six, whom she made seneschal of the kingdom. He and the constable Muzio Attendolo Sforza completely dominated her, and the turbulent barons wished to provide her with a husband who would be strong enough to break her favourites yet not make himself king. The choice fell on James of Bourbon, a relative of the king of France, and the marriage took place in 1413. But James at once declared himself king, had Alopo killed and Sforza imprisoned, and kept his wife in a state of semi-confinement; this led to a counteragitation on the part of the barons, who forced James to liberate Sforza, renounce his kingship, and eventually to quit the country. The queen now sent Sforza to re-establish her authority in Rome, whence the Neapolitans had been expelled after the death of Ladislaus.
Sforza entered the city and obliged the condolliere Braccio da Montone, who was defending it in the pope's name, to depart (1416). But when Oddo Colonna was elected pope as Martin V, he allied himself with Joanna, who promised to give up Rome, while Sforza returned to Naples. The latter found, however, that he had lost all influence with the queen, who was completely dominated by her new lover Giovanni (Sergianni) Caracciolo. Hoping to re-establish his position and crush Caracciolo, Sforza favoured the pretensions of Louis III of Anjou, who wished to obtain the succession of Naples at Joanna's death, a course which met with the approval of the pope. Joanna refused to adopt Louis owing to the influence of Caracciolo, who hated Sforza; she appealed for help instead to Alphonso of Aragon, promising to make him her heir. War broke out between Joanna and the Aragonese on one side and Louis and Sforza, supported by the pope, on the other. After much fighting by land and sea, Alphonso entered Naples, and in 1422 peace was made. But dissensions broke out between the Aragonese and Catalans and the Neapolitans, and Alphonso had Caracciolo arrested; whereupon Joanna, fearing for her own safety, invoked the aid of Sforza, who with difficulty carried her off to Aversa. There she was joined by Louis whom she adopted as her successor instead of the ungrateful Alphonso. Sforza was accidentally drowned, but when Alphonso returned to Spain, leaving only a small force in Naples, the Angevins with the help of a Genoese fleet recaptured the city.
For a few years there was peace in the kingdom, but in 1432 Caracciolo, having quarrelled with the queen, was seized and murdered by his enemies. Internal disorders broke out, and Gian Antonio Orsini, prince of Taranto, led a revolt against Joanna in Apulia; Louis of Anjou died while conducting a campaign against the rebels (1434), and Joanna herself died on the 11th of February 1435, after having appointed his son Rene her successor. Weak, foolish and dissolute, she made her reign one long scandal, which reduced the kingdom to the lowest depths of degradation.
Her perpetual intrigues and her political incapacity made Naples a prey to anarchy and foreign invasions, destroying all sense of patriotism and loyalty both in the barons and the people.
She was married to William, son of Leopold III of Austria, but widowed at the age of 41.
She married again to James of Bourbon, Count of La Marche. The marriage took place in 1413. She had no children.