President Barack Obama's administration has unveiled plans to significantly narrow the circumstances in which the US would use nuclear weapons.But its Nuclear Posture Review warned countries breaking the rules remain potential targets.
The US strategy document also raised concerns about a "lack of transparency" in China's nuclear programme.
The review comes two days before Mr Obama and his Russian counterpart sign a landmark nuclear arms reduction pact.
The deal, agreed last month, commits Russia and America to big cuts in nuclear warheads and would replace the 1991 Strategic Arms Reduction Treaty (Start), which expired last December.
The Nuclear Posture Review, published on Tuesday, outlines plans for "achieving substantial further nuclear force reductions" beyond the new treaty.
Every president since 1991 conducts such a review - the last one took place in 2001 at the start of George W Bush's administration.
But Mr Obama set high expectations when he declared America's commitment to seek the peace and security of a world without nuclear weapons in Prague last year.
For the first time, the US is ruling out a nuclear response to attacks on America involving biological, chemical or conventional weapons.
But this comes with a big caveat: countries will only be spared a US nuclear response if they comply with the Nuclear Non-Proliferation Treaty - this does not include Iran and North Korea.
"[Tehran and Pyongyang's] continued defiance of international norms and agreements will lead only to their further isolation and increasing international pressure," the document notes.
Tehran insists its nuclear programme is peaceful, but its refusal to adhere to international demands has raised fears of a possible strike on its nuclear facilities by the US or Israel.
Defence Secretary Robert Gates outlined the Nuclear Posture Review at a Pentagon briefing on Tuesday and said it would pave the way to a nuclear-free world.
The document said America would only use nuclear arms in "extreme circumstances", and committed it to not developing any new nuclear warheads.
But the review also said the US would maintain its conventional arsenal to "reassure our non-nuclear allies and partners worldwide of our security commitments".
The US defence department document said China's nuclear arsenal remained much smaller than those of Russia and America.
"But the lack of transparency surrounding its nuclear programmes - their pace and scope, as well as the strategy and doctrine that guides them - raises questions about China's future strategic intentions," it noted.
The US president is also hosting a nuclear non-proliferation summit in Washington next week, which is set to be attended by dozens of world leaders.
Mr Obama won the Nobel Peace Prize last year, in part for his vision of a nuclear-free world.
The BBC's Kim Ghattas, in Washington, says the new US nuclear policy reflects a changing world.
While nuclear weapons have been useful to achieve a balance of power with countries like Russia or China, modern threats require a more nimble defence strategy, our correspondent says.
But the Obama administration's strategy review is still likely to be criticised by both sides of the political divide, she adds.
The new nuclear pact - which Mr Obama is due to sign on Thursday in Prague with Russian President Dmitry Medvedev - commits the former Cold War rivals to significant cuts in their weapons' stockpiles.
The treaty would restrict both Moscow and Washington to a maximum of 1,550 warheads each, about 30% less than currently allowed, the US says.
But Russia drew some lines in the sand on Tuesday, warning it could pull out if it decided a US missile defence shield, proposed for Europe, threatened its security.
