Born in Alkmaar, the son of a schoolmaster; later records of his age place his date of birth between 1615 and 1618. He trained, according to Houbraken, with the still-life painter Evert van Aelst in Delft.
In 1636 he entered the Alkmaar guild, but he is recorded at Rotterdam in 1639 and 1640, and soon afterwards moved to Delft, where he entered the guild in 1642. By 1652 he had settled in Amsterdam. He started as a history painter and portraitist, but in the late 1640s, with Gerard Houckgeest, he evolved a style of architectural painting with a new directness in the observation of light and atmosphere.
He also painted some domestic interiors, harbour views and market scenes. After 1658 he suffered financial troubles, placing himself under contract with an Amsterdam notary in 1660 to paint in return for his keep. His wife was banished from Amsterdam for theft, while her daughter (by a previous marriage) was imprisoned for the same offence. De Witte was said to have committed suicide, his body being recovered from a frozen canal in 1692, eleven weeks after his disappearance.