The transformation of the Gothic castle into a Renaissance residence took place primarily under Zachariáš of Hradec. As a member of the Hradec branch of the Vítkovec family, he acquired the Moravian domains as part of the inheritance from his father Adam I. of Hradec. A year later, in 1551, the new Telč owner took part in the famous journey of Czech noblemen to Genova in Italy. A report from that time even mentions him as the fourth most important nobleman and speaks highly of his elaborate armament and cohort. Zachariáš comes back influenced by Italian Renaissance and shortly after his return, starts, as with the other participants of the journey, to transform his residence.

The transformation of the Telč Castle was performed in two stages under the guidance of Italian masters. In some of the Chateau's interiors, older cell-vaults with original decorations have been preserved. They were made by the stonemason and architect Leopold Esterreicher from the nearby Slavonice. Whereas Zachariáš acquired the Moravian estates, his brother Jáchym inherited the South Bohemian estates, including the family residence in Jindřichův Hradec. At both chateaus – in Telč and in Jindřichův Hradec – the same architects and artists were working. The chateaus are thus close in their architecture and the decorations of their splendid interiors.
The rebuilding of the Chateau and other building activities were extremely costly. They were enabled by the then good economic situation of the Telč domain and particularly the high yields from the silver mines whose majority were brought to Zachariáš by his first wife Kateřina of Valdštejn (Wallenstein) as part of her dowry. The elaborate Renaissance transformation of the oldest part of the Telč Chateau was carried out in 1553 when Zachariáš of Hradec married Kateřina of Valdštejn. We can therefore find many coats of arms of the newlyweds throughout the Chateau's portals, facades and interiors.

The grandest interior of the Telč Chateau is the Golden Hall, stretching across the entire wing of the younger Renaissance Northern Palace. Low arcades rim the Renaissance garden. The architect who designed the final appearance of the entire precinct was probably Baldassare Maggi of Arogni. The last building activity was the construction of the sepulchral All Saints Chapel (1580).

The original appearance of most of the premises was not changed even by the last owners and Telč thus ranks among the few intact Czech and Moravian Renaissance Chateaus. The Chateau was never sold but it was always passed on from one family to another. At the beginning of the 17th century, Telč was acquired by the Slavata family. A member of the family of the Lords of Hradec – Lucie Otílie - married Vilém Slavata of Chlum and Košumberk. The Slavata period is documented by some paintings at the Chateau – particularly the portraits. The most important item is the large oil painting depicting the Prague Defenestration of 1618 in quite a peculiar way. The efforts of the Slavata family to make the Telč inhabitants convert to Catholicism is proven by the Baroque Jesuit Church of the Name of Jesus located very close to the Chateau. The later owners of the domain – the family of Liechtenstein of Kastelkorn and the Podstatský family of Liechtenstein made only minor changes to the Chateau. They paid more attention to the Chateau's Park where they later built a magnificent Empire greenhouse.