Leaders from 46 other nations will attend the meeting, aimed at safeguarding unsecured uranium and separated plutonium stockpiles and averting extremist groups acquiring nuclear weapons.
On the eve of the summit, which will be the largest chaired by a US president in 65
years, Obama said the “single biggest threat to US security … would be the possibility of a terrorist organisation obtaining a nuclear weapon".
"This is something that could change the security landscape of this country and around the world for years to come."
The White House will seek concrete commitments from world leaders on securing stockpiles of separated plutonium and uranium, to ensure that they cannot be stolen, smuggled or sold to extremists.
As well as presiding over the summit, Obama will hold a string of bilateral meetings with world leaders.
To kick off his counter-proliferation drive, Obama met Kazakhstan's President Nursultan Nazerbayev and South African President Jacob Zuma.
Kazakhstan handed over Soviet-era nuclear weapons after the end of the Cold War, but is a key player in Washington as it bills itself as the world's top exporter of uranium.
Obama last week signed a landmark disarmament treaty with Russia and laid out a new US nuclear strategy limiting how Washington could use atomic weapons.
The conference is also a precursor to the United Nations Non-Proliferation Treaty review conference next month, seen as another important moment in heading off a future nuclear arms race.