Whiston, the son of a parish priest from Norton in England, was educated at Cambridge University, where he came to the attention of Isaac Newton. He was selected, on Newton's recommendation, to succeed him as Lucasian Professor of Mathematics (1703) and to edit his Arithmetica universalis (1707; Universal Arithmetic). In 1710 he was dismissed from the university for his unorthodox religious belief in the Arian heresy, after which time he supported himself by giving public lectures on popular science.

Whiston's chief scientific work, A New Theory of the Earth (1696), was praised by Newton and by John Locke. In this Whiston followed the tradition recently established by Thomas Burnet in attempting to explain biblical events, such as the Creation, scientifically. The Flood, he believed, was caused by a comet pasing close to the Earth on 28 November 2349 bc. This put stress on the Earth's crust, causing it to crack and allow the water to escape and flood the Earth.