Kettler was born near Anröchte, Kreis Soest, of an old Westphalian noble family and the ninth child of the German knight Gotthard Kettler zu Melrich (mentioned 1527–1556) and his wife Sophie of Nesselrode.

In 1559, during the Livonian War (1558–1582), he succeeded Wilhelm von Fürstenberg as Master of the Teutonic Order in Livonia.

When the Livonian Confederation came under increasing pressure from Ivan IV of Russia, Kettler converted to Lutheranism and secularised Semigallia and Courland.

[2] Following the duke's proposal in 1567, the regional assembly (landtag) decided to build 70 new churches and 8 schools in the remote areas of Duchy where many peasants still lived and died unbaptized.

The daughter Anna Kettler married the Polish-Lithuanian prince Albrecht Radziwiłł, the son of Mikołaj "the Black" Radziwiłł, the daughter Elisabeth Kettler married the Adam Wenceslaus, Duke of Cieszyn of Duchy of Teschen.