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Because of the short half-life of all fermium isotopes, all that may have been present on the Earth during its formation has long since decayed away.

Einsteinium and fermium did occur in the natural nuclear fission reactor at Oklo, but no longer exist. Fermium is produced as the result of multiple neutron captures in lighter elements, such as uranium and curium, followed by successive beta decays. The probability of such events increases with increased neutron flux, and nuclear explosions are the most powerful neutron sources on Earth. Fermium is also produced by the bombardment of lighter actinides with neutrons in nuclear reactors or accelerators. Fermium-257 is the heaviest isotope that is obtained via neutron capture, and can only be produced in nanogram quantities. The major source is the 85 MW High Flux Isotope Reactor (HFIR) at the Oak Ridge National Laboratory in Tennessee, USA. In a HFIR "campaign", tens of grams of curium are irradiated to produce heavier actinides and picogram quantities of fermium. The quantities of fermium produced in 20-200 kiloton thermonuclear explosions are believed to be of the order of milligrams, although it is mixed in with a huge quantity of debris. Forty picograms of 257Fm were recovered from 10 kilograms of debris from the 'Hutch' nuclear test in 1969. After production, fermium must be separated from debris and a host of other actinides and lanthanide fission products by solvent extraction, ion exchange, etc.). The annual reactor production of fermium-257 is in the picogram range. However, pure 255Fm (half-life 20 hours) can be easily isolated by "milking" the beta-decay daughter of pure 255Es (half-life 39.8 days).

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