He was educated at Graz, Bologna and Rome.
In 1521 he accompanied Thomas Cajetan (whom the pope had sent to Hungary to preach a crusade against the Turks) to Buda as his interpreter. During his absence the Mohács catastrophe took place, and Nádasdy only returned to Hungary in time to escort the queen-widow from Komárom to Pozsony. He was sent to offer the Hungarian crown to the archduke Ferdinand, and on his coronation (3 November 1527) was made commandant of Buda.
In 1528 with the help of Count György Cseszneky, commander of Tata Nádasdy occupied Győr for Ferdinand.
In 1533 his jealousy of the dominant influence of Lodovico Gritti caused him to desert John for Ferdinand, to whom he afterwards remained faithful. He was endowed with enormous estates by the emperor, and from 1537 onwards became Ferdinand"s secret but most influential counsellor.
He did his utmost to promote education, and the school which he founded at Újsziget, where he also set up a printing press, received a warm eulogy from Philip Melanchthon. In 1540 Nádasdy was appointed iudex curie regie.
In 1547 he presided over the Diet of Nagyszombat, and finally, in 1559, was elected palatine by the diet of Pozsony (now Bratislava, Slovakia).
In his declining years he aided the heroic Miklós Zrinyi against the Ottomans.
On the capture of Buda by Suleiman the Magnificent, Nádasdy went over to King John I. In 1530 he successfully defended Buda against the imperial troops. Subsequently, as Ban of Croatia-Slavonia, he valiantly defended that border province against the Turks.
In 1525 he became a member of the council of state and was sent by King Louis II to the diet of Speyer to ask for help in the imminent Turkish war.