The agreement comes days after Georgian authorities revealed details of a case in which a Russian national was arrested for attempting to sell weapons-grade uranium in the former Soviet republic.
Under the deal signed by Georgian Foreign Minister Gela Bezhuashvili and US ambassador to Tbilisi John Tefft, Georgia will set up a nuclear security agency and boost border controls with US help, a foreign ministry official said.
Oleg Khintsagov, a Russian national, was arrested in February last year in a joint operation by Georgian police and the United States' Federal Bureau of Investigation (FBI) for trying to sell 100 grams (3.5 ounces) of highly-enriched uranium.
The International Atomic Energy Agency (IAEA), the UN's nuclear watchdog, reacted with concern to the case, the latest of several smuggling incidents in the former Soviet Union.