Wilhelm Kettler was the youngest son of Gotthard Kettler and his wife Anna of Mecklenburg. After their father's death in 1587, Wilhelm and his brother Friedrich inherited the Duchy of Courland. The brothers decided to divide the duchy between themselves. Wilhelm ruled the Courland portion with the seat in Kuldīga. In 1609 he married Princess Sophia of Brandenburg-Prussia (1582–1610), daughter of Albert Frederick, Duke of Prussia, receiving as a dowry the territory of Grobiņa. Due to conflicts with the nobility, he lost the duchy in 1617 and emigrated.
He died in the Kukulva abbey in Pomerania on 7 April 1640. His son, Duke Jacob Kettler of Courland, had his remains returned to Courland in 1642. He was interred in the duchy tomb on 23 February 1643.