President Barack Obama wants to cut the nuclear arsenals of the United States and Russia by one-third.
In a speech at the Brandenburg Gate in Berlin on Wednesday he called for reductions in the number of tactical warheads deployed in Europe.
The gate was the location where Presidents Ronald Reagan and John F Kennedy gave Cold War speeches denouncing the division of Berlin in the Cold War.
Mr Obama also pledged to boost efforts to close the Guantanamo Bay detention centre and tackle climate change, the BBC reports.
Mr Obama said the Brandenburg Gate was a symbol that "no wall can stand against the yearnings for justice... that burn in the human heart".
"Today's threats are not as stark as they were half a century ago, but the struggle for freedom and security and human dignity, that struggle goes on.
"We may no longer live in fear of global annihilation but so long as nuclear weapons exist, we are not truly safe. I intend to seek negotiated cuts with Russia to move beyond Cold War nuclear postures."
Under a treaty which the US signed with Russia in 2010, each side is allowed a maximum of 1550 warheads and no more than 700 deployed launchers.
The new limit on delivery systems is less than half the ceiling of 1600 specified in the original Start treaty from 1991.
Shortly before Mr Obama spoke, Russia's President Vladimir Putin was quoted as saying that Moscow "cannot allow the balance of the system of strategic deterrence to be disturbed or the effectiveness of our nuclear force to be decreased".
Earlier, Mr Obama met German Chancellor Angela Merkel, who criticised the broad scope of US surveillance programmes, including Prism the phone and internet programme.
"We do see the need for gathering information, but there is a need for due diligence and proportionality."
Mrs Merkel grew up in Communist East Germany, where police surveillance was widespread. She acknowledged that the internet "enables enemies of a free liberal order to use and abuse and bring threats to all of us", but said "an equitable balance must be struck".
