Californium was first produced by Stanley G. Thompson, Glenn T. Seaborg, Kenneth Street, Jr. and Albert Ghiorso working at the University of California, Berkeley, in 1950. They bombarded atoms of curium-242 with helium ions using a device known as a cyclotron. This produced atoms of californium-245, an isotope with a half-life of about 45 minutes, and a free neutron.

Californium-252, an isotope with a half-life of about 2.6 years, is a very strong neutron source. One microgram (0.000001 grams) of californium-252 produces 170,000,000 neutrons per minute. It is being used as a neutron source to identify gold and silver ores through a technique known as neutron activation. It is also being used in devices known as neutron moisture gauges that are used to find water and oil bearing layers in oil wells.

A few compounds of californium have been produced and studied. They include: californium oxide (CfO₃), californium trichloride (CfCl₃) and californium oxychloride (CfOCl).

Californium's most stable isotope, californium-251, has a half-life of about 898 years. It decays into curium-247 through alpha decay or decays through spontaneous fission.