He was the oldest son of Cornelis Fransz de Witt (1545–1622), 16-fold burgomaster of Dordrecht and Johanna Heijmans.
Andries married Elizabeth van den Honert in 1604, with whom he had 10 children.
De Witt studied law at the University Leiden, traveled to Germany, Switzerland, France and England for several years, and then held various offices in Dordrecht, finally that of Pensionary.
In the dispute between the governor Maurice, Prince of Orange and the provincial advocate Johan van Oldenbarnevelt, he sided with Moritz.
As a Grand Pensionary De Witt acted without initiative, without his own influence on either internal or external business.