It was founded in 1890 by Polish Jews who wanted a township independent of Baron Edmond de Rothschild's aid. They called their settlement Rehovot ("wide expanses") a name based on Genesis 26:22. In 1906 they were joined by immigrants from Yemen.

These early settlers worked hard to make Rehovot the prosperous town it is today. They planted vineyards, almond orchards and citrus groves. Rehovot has become one of Israel's main citrus centers, especially since nearby Ashdod was opened as a port in 1965. They withstood agricultural failures, plant diseases, marketing problems and attack from hostile Arabs.

Between 1914 and 1991 the population rose for 955 to 81,000, and the area of the town more than doubled. In 1995, there is an estimated 337,800 Jews and non-Jews living in the greater Rehovot area. In 1932 an Agricultural Research Station was transferred there from Tel Aviv; 30 years later it became the Department of Agriculture of the Hebrew University of Jerusalem. In 1934 Chaim Weizmann built the Sieff Institute, which later became the Weizmann Institute of Science (see picture), in Rehovot. He and his wife are buried in the beautiful grounds of the Institute.

Industries in the town include food processing and the making of artificial leather and chemicals.

Rehovot is a quiet secluded city known primarily for the Weizmann Institute of Science. The Institute's scientific staff conducts research in natural sciences, and projects include research on cancer, aging, environment, computers, etc.