Born in Ishpeming, Michigan, Seaborg graduated in 1934 and gained his doctorate in 1937 at the University of California. He rose to become full professor in the Berkeley faculty in 1945.

Over the period 1948–58 Seaborg and his collaborators extended the periodic table beyond uranium (element 92) – hence the term ‘transuranics’ applied to artificial elements with atomic numbers higher than 92. Chief among his collaborators in the early days was Edwin McMillan (with whom he shared the Nobel Prize for chemistry in 1951), who with Philip Abelson had discovered the first transuranic element – neptunium (element 93) – in the spring of 1940. Neptunium was found to be a beta-particle emitter and it was thus expected that its decay product should be a transuranic element – the next in the series. In December 1940 Seaborg, McMillan, and their collaborators isolated element 94 – plutonium. It was realized that the transuranics formed a special series – the actinide transition series of elements, similar to the lanthanide series of rare-earth elements. Thus Seaborg and his coworkers were able to predict the chemical properties of further then-unknown transuranics and enabled them to be isolated. Seaborg's name is associated with the discovery or first isolation of a number of transuranics:

• Element 93 neptunium 1940

• Element 94 plutonium 1940

• Element 95 americium 1944

• Element 96 curium 1944

• Element 97 berkelium 1949

• Element 98 californium 1950

• Element 101 mendelevium 1955

• Element 102 nobelium 1958

It should be noted that all of these discoveries are correctly attributed to groups or teams of researchers and that attribution has been disputed in the past. In particular the first, unconfirmed, report of element 102 was in 1957 by an international group of physicists working at the Nobel Institute in Stockholm. The Berkeley team subsequently confirmed the discovery the next year. Similar work to Seaborg's was done in the former Soviet Union by Georgii Flerov.

Another discovery with which Seaborg is associated is the isolation of the isotope uranium–233 from thorium (1941). This may be an alternative source of fuel for nuclear fission – a route to nuclear energy that is still relatively unexplored.

The work on elements was directly relevant to the World War II effort to develop an atomic bomb, and from 1942 until 1946 Seaborg was on leave to the University of Chicago metallurgical laboratory, where he was made head of the laboratory's chemical-separation section. It is said that he was influential in determining the choice of plutonium rather than uranium in the first atomic-bomb experiments.

Seaborg went on to become chancellor of the University of California from 1958 to 1962 and was then chair of the US Atomic Energy Commission until 1971. Element 106, synthesized in 1974, was named seaborgium in his honor.