Obama said the agreement recognized a "cruel irony of history": After surviving a Cold War arms race and the threat of nuclear war, the world now must confront the even larger danger of nuclear terrorism.
Wealthier nations will help defray the cost of the effort for poorer ones. The United States has budgeted $3 billion in the current fiscal year for better securing nuclear material.
Obama acknowledged that there is no way to enforce the agreement except through the good intentions of world leaders who, he said, share his view of the urgency of the program.
"Terrorist networks such as Al Qaeda have tried to acquire the material for a nuclear weapon, and if they ever succeed, they would surely use it," Obama said. "Were they to do so, it would be a catastrophe for the world."
The four-year plan spelled out in a statement at the end of the two-day conference would require action at thousands of civilian nuclear installations and military and university sites at a likely cost of billions of dollars.
Although regional cooperation is important to halt nuclear smuggling, countries in the Middle East and South Asia may be reluctant to work with neighbors who also are rivals. Some are wary of sharing information about their sites with other world powers or even world organizations such as the United Nations' nuclear watchdog, the International Atomic Energy Agency.