His father, Jaroslav Lev of Rožmitál, was a brother-in-law of King George of Poděbrady.
In this position, Zdeněk administered Bohemia, as King Vladislaus II spent most of his time in Hungary.
However, his successor lasted for only two years, and in 1525 he was re-appointed and some of his friends were also elevated to high office.
In the meantime, the number of his Catholic enemies grew; in particular the House of Rosenberg turned against him, due to a dispute over the inheritance of Český Krumlov.
In 1526, Louis II fell in the Battle of Mohács, ending Jagiellon rule in Bohemia.
From then on, he concerned himself solely with the administration of his properties at Horní Blatná, Rožmitál, Velhartice, Klenová, Opálka, Lysá, Mšeno, Chbany, Zdechovice, Rýzmberk, Skály and Poděbrady.