Born in Sneek, De Sitter studied mathematics at the University of Groningen and then joined the Groningen astronomical laboratory. He worked at the Cape Observatory in South Africa (1897-1899). Then, in 1908, de Sitter was appointed to the chair of astronomy at Leiden University. He was director of the Leiden Observatory from 1919 until his death.
De Sitter made major contributions to the field of physical cosmology. He co-authored a paper with Albert Einstein in 1932 in which they argued that there might be large amounts of matter which do not emit light, now commonly referred to as dark matter. He also came up with the concept of the de Sitter universe, a solution for Einstein's general relativity in which there is no matter and a positive cosmological constant. This results in an exponentially expanding, empty universe. De Sitter was also famous for his research on the planet Jupiter.
Named after him