In 1544, at the age of nine, he switched to a Catholic school for young nobles at the court of Bishop Wolfgang of Passau.

On 23 April 1551, at the age of sixteen, William was declared an adult by a decree of Emperor Ferdinand I.

He took up the administration of the family's possessions and chose as his residence Český Krumlov Castle, which he remodeled in the Renaissance style.

From 1552 to 1556, he fought a court case against Henry IV of Plauen, the High Chancellor of Bohemia, about their precedence in Bohemian society.

Their aim was to recapture Szigetvár, which William's brother-in-law Nikola Šubić Zrinski had lost to the Turks.

In 1572, he negotiated with Emperor Maximilian II, the leader of the Holy League about the next step to take in the ongoing war with then Ottoman Empire.

In addition to his high political office, William was actively promoting science, literature, music and architecture.

Many humanists such as the Flemish mineralogist, physician and naturalist Anselmus de Boodt (1550-1632) were active at his court.

In 1573, William expanded the Rosenberg Palace his uncle Peter V had built inside the Prague Castle, using designs made by the architect Ulrico Aostalli.

William died in 1592 and was buried in the St. Vitus Church in Český Krumlov, next to his third wife, Anna Maria of Baden.

By marrying German imperial princesses, he gained political influence outside Bohemia, which benefitted his diplomatic efforts.