Isabella Jagiellon (Hungarian: Izabella királyné; Polish: Izabela Jagiellonka) (18 January 1519 – 15 September 1559) was Queen consort of the "Eastern Hungarian Kingdom" as the wife of John Zápolya.

Born in Kraków to King Sigismund I the Old and Bona Sforza, Princess of Milan, Isabella was brought up in the Polish royal court. Her mother taught her the Italian language, so she became an educated young lady, who spoke four languages.

In 1539 Isabella was married to John Zápolya, Voivode of Transylvania and King of Hungary. Their son John Sigismund Zápolya was born on 8 July 1540. Her husband died two weeks after the child was born.

John Zápolya had been elected King in 1526, but his claim had been challenged by Archduke Ferdinand of Austria. John had sustained his claim only by gaining support from the Ottoman Empire at the price of declaring the Kingdom a vassal of the Ottoman Empire. In 1538, Ferdinand, who held western Hungary, had forced John Zápolya, who was then childless, to recognize him as his successor to the whole kingdom in the Treaty of Nagyvárad.

But in 1540, the Hungarian Diet elected the infant John Sigismund as King of Hungary. This broke the treaty, and Ferdinand invaded Hungary. Isabella struggled to rule Hungary as Queen dowager for her son, the electus rex (elected King). Frater George Martinuzzi, appointed by John as regent, opposed her.

In 1541, Martinuzzi invited Ottoman Sultan Suleiman to defend his vassal from Ferdinand. Suleiman countered Ferdinand’s invasion with Ottoman forces which occupied Buda. In 1541, Isabella met with the Sultan, who allocated Transylvania and eastern Royal Hungary to her son John II Sigismund, with her as guardian, and holder of the personal domain of Siebenburgen, with her residence at Alba Iulia. However, the real governor was Martinuzzi.

Isabella and Martinuzzi remained at odds, and a few years later, Martinuzzi began secretly negotiating with King Ferdinand. In 1549 they reached an agreement. Isabella was to give up Siebenburgen. In return she was to receive the Principality of Opelin in Silesia, and in addition all that had been left her by her husband. Ferdinand was also to provide for John II Sigismund, who would be Ferdinand's vassal as Prince of Transylvania, and later marry one of his daughters.

Isabella balked, but Martinuzzi was in control. In 1551, she agreed to the Treaty of Weissenburg, which ceded Transylvania and Royal Hungary to Ferdinand, whose armies had entered Transylvania. Ferdinand was also to receive the royal crown and regalia.

According to the legend, when Isabella stopped to have a rest at the gates of Meszes, she cut the abbreviation of her op into the bark of an old oak tree: SFV – Sic fata volunt ("It is the will of fate").

However, Ferdinand was unable to defend the country from Ottoman attacks. In 1556, the Transylvanian Diet invited her to return to the country with John II Sigismund and her advisor, Mihály Csáky. Isabella set up her Transylvanian chancellery with the help of Csáky, and the new state started to function. She reigned in the new state with her son until her death in Alba Iulia in 1559.

Isabella is notable as being "the first ruler to issue an edict of universal toleration" in religion. The edict was passed in 1558, preceding the more famous Edict of Nantes (1598), by forty years.