He was the son of Count Palatine Philip William of Neuburg and Elisabeth Amalie of Hesse-Darmstadt and was born in Düsseldorf, where he resided, rather than in Heidelberg, which had been largely destroyed by French troops during the Nine Years' War.

During the War of the Spanish Succession Johann Wilhelm received also the Bavarian Upper Palatinate, which was returned to Bavaria in 1714.

Having no son, Johann Wilhelm was succeeded by his brother Charles III Philip, Elector Palatine.

On 25 October 1678, in Wiener Neustadt, Johann Wilhelm married Archduchess Maria Anna Josepha of Austria.

[5] Historians believed incorrectly that shortly after her arrival, she contracted syphilis from her adulterous husband, which might have explained why Anna Maria Luisa and Johann Wilhelm failed to produce any children.

A patron of the arts, she bequeathed the Medicis’ large art collection, including the contents of the Uffizi, Palazzo Pitti, and the Medicean villas, which she inherited upon the death of her brother Gian Gastone in 1737, and her Palatine treasures to the Tuscan state, on the condition that no part of it could be removed from the capital Florence.