Berkelium was first produced by Stanley G. Thompson, Glenn T. Seaborg, Kenneth Street, Jr. and Albert Ghiorso working at the University of California, Berkeley, in December, 1949. They bombarded an isotope of americium, americium-241, with alpha particles with a device called a cyclotron. This created berkelium-243 and two free neutrons.

Berkelium's most stable isotope, berkelium-247, has a half-life of about 1,380 years. It decays into americium-243 through alpha decay.

The first visible amounts of a berkelium compound, berkelium chloride (BkCl₃) was produced in 1962 and weighed about 3 billionths of a gram (0.000000003 grams). Berkelium oxychloride (BkOCl), berkelium fluoride (BkF₃), berkelium dioxide (BkO₂) and berkelium trioxide (BkO₃) have been identified and studied with a method known as X-ray diffraction.

Since only small amounts of berkelium have ever been produced, there are no known uses for berkelium and its compounds outside of basic scientific research.