Nucleosynthesis is the process that creates new atomic nuclei from pre-existing nucleons (protons and neutrons) and nuclei. According to current theories, the first nuclei were formed a few minutes after the Big Bang, through nuclear reactions in a process called Big Bang nucleosynthesis. After about 20 minutes, the universe had expanded and cooled to a point at which these high-energy collisions among nucleons ended, so only the fastest and simplest reactions occurred, leaving our universe containing hydrogen and helium. The rest is traces of other elements such as lithium and the hydrogen isotope deuterium. Nucleosynthesis in stars and their explosions later produced the variety of elements and isotopes that we have today, in a process called cosmic chemical evolution. The amounts of total mass in elements heavier than hydrogen and helium (called 'metals' by astrophysicists) remains small (few percent), so that the universe still has approximately the same composition.

Stars fuse light elements to heavier ones in their cores, giving off energy in the process known as stellar nucleosynthesis. Nuclear fusion reactions create many of the lighter elements, up to and including iron and nickel in the most massive stars. Products of stellar nucleosynthesis remain trapped in stellar cores and remnants except if ejected through stellar winds and explosions. The neutron capture reactions of the r-process and s-process create heavier elements, from iron upwards.

Supernova nucleosynthesis within exploding stars is largely responsible for the elements between oxygen and rubidium: from the ejection of elements produced during stellar nucleosynthesis; through explosive nucleosynthesis during the supernova explosion; and from the r-process (absorption of multiple neutrons) during the explosion.

Neutron star mergers are a recently discovered major source of elements produced in the r-process. When two neutron stars collide, a significant amount of neutron-rich matter may be ejected which then quickly forms heavy elements.

Cosmic ray spallation is a process wherein cosmic rays impact nuclei and fragment them. It is a significant source of the lighter nuclei, particularly ³He, ⁹Be and ^10,11B, that are not created by stellar nucleosynthesis. Cosmic ray spallation can occur in the interstellar medium, on asteroids and meteoroids, or on Earth in the atmosphere or in the ground. This contributes to the presence on Earth of cosmogenic nuclides.

On Earth new nuclei are also produced by radiogenesis, the decay of long-lived, primordial radionuclides such as uranium, thorium, and potassium-40.