During the First Stadtholderless Period, De Witt was an influential member of the Dutch States Party, and was in opposition to the House of Orange.

De Witt's mother was Anna van den Corput (1599–1645), niece of Johannes Corputius, an influential Dutch military leader and cartographer.

Through the marriage of one of his other uncles to Margaretha of Nassau, daughter of Anna Johanna of Nassau-Siegen, De Witt was a distant relative of William of Orange-Nassau.

Compelled by illness to leave the Dutch States Navy, he found on his return to Dordrecht that the Orangists were in the ascendant, and he and his brother were the objects of popular suspicion and hatred.

The couple had five children:[8] He was arrested on false accusations of treason, but did not confess despite heavy torture and was ultimately unlawfully condemned to be banished.

[5] He was assassinated by the same carefully organised lynch mob that killed his brother on the day he was to be released, victim of a conspiracy by the Orangists Johan Kievit and Lieutenant-Admiral Cornelis Tromp.