Agreed in April after more than four years of negotiation, the accord would take effect from 6:00pm (0900 GMT) with an exchange of diplomatic notes, Seoul’s foreign ministry said.
It replaces an existing 1974 accord and was struck after four-and-a-half years of intense negotiations.
South Korea had wanted to develop uranium enrichment and reprocessing capabilities in order to address concerns about energy security and the management of spent nuclear reactor fuel.
But the US opposed the move, arguing that such capabilities could be used to produce weapons-grade nuclear material and therefore posed a proliferation risk.
The deal does leave the door open to reprocessing sometime in the future, by allowing South Korea to conduct “research” into spent fuel management.
That includes research into “pyroprocessing” — a new technology considered largely proliferation-resistant since the product is thermally and radioactively far too hot to use for a weapon.
South Korea, which has no nuclear weapons, is a key US military ally. Analysts say Washington’s concerns on allowing reprocessing stem less from a distrust of Seoul’s ultimate intentions than from the impact it might have on negotiations with other countries.
There are also worries that wider concessions on reprocessing could further complicate efforts to roll back North Korea’s nuclear weapons programme.
The North has staged three successful atomic tests and demands that the US recognise it as a nuclear power.
South Korea — the world’s fifth-largest consumer of nuclear energy and home to more than 20 nuclear reactors — is also seeking to become a key exporter of atomic power plants.