Humanity is "just one misunderstanding away from nuclear annihilation", according to the head of the United Nations in a dire warning.
It comes as America accused Russia of using Ukraine's biggest nuclear power station, which it seized early on in the war, as a "nuclear shield" during its attacks.
US Secretary of State Antony Blinken said Washington was "deeply concerned" that Moscow was now using the Zaporizhzhia plant as a military base and firing at Ukrainian troops from around it.
He said: "The Ukrainians cannot fire back lest there be a terrible accident involving the nuclear plant."
Meanwhile, Mr Guterres said "geopolitical weapons are reaching new highs", nearly 13,000 nuclear weapons are in arsenals globally, and countries seeking "false security" are spending hundreds of billions of dollars on "doomsday weapons".
He said: "All this at a time when the risks of proliferation are growing and guardrails to prevent escalation are weakening."
Mr Guterres spoke of the need to address the "simmering tensions" in the Middle East and Asia.
"By adding the threat of nuclear weapons to enduring conflicts, these regions are edging towards catastrophe. We need to redouble our support for dialogue and negotiation," he continued.
He said today, humanity was "just one misunderstanding, one miscalculation away from nuclear annihilation".
He was speaking at the UN to review the landmark Non-Proliferation Treaty (NPT), which came into force in 1970, aiming to prevent the spread of nuclear weapons and eventually achieve a nuclear-free world.
He told ministers, officials and diplomats in New York that the month-long conference is taking place "at a critical juncture for our collective peace and security" and "at a time of nuclear danger not seen since the height of the Cold War".
"The world is worried that the threat of the catastrophe of use of nuclear weapons has emerged once again," he told the gathering, and "the path to a world without nuclear weapons has suddenly become even harder".
Which nations have nuclear weapons?
Under the NPT, the five original nuclear powers - the US, China, Russia (then the Soviet Union), the UK and France - agreed to negotiate towards eventually eliminating their arsenals.
And nations without nuclear arms promised not to acquire them in exchange for a guarantee to be able to develop nuclear energy for peaceful purposes.
It has the widest adherence of any arms control agreement, with 191 countries as members.
India and Pakistan, which did not join the NPT, went on to have nuclear weapons programmes, as did North Korea, which ratified the pact but later announced it was withdrawing.
Non-signatory Israel is believed to have nuclear weapons but has not confirmed or denied it.
The New York meeting is "an opportunity to hammer out the measures that will help avoid certain disasters, and to put humanity on a new path towards a world free of nuclear weapons," Mr Guterres said.
He called on nations to reinforce and reaffirm "the 77-year-old norm against the use of nuclear weapons"; work relentlessly towards the elimination of nuclear weapons with new commitments to reduce arsenals; and promote the peaceful use of nuclear technology.
"Future generations are counting on your commitment to step back from the abyss," Mr Guterres said.
"This is our moment to meet this fundamental test and lift the cloud of nuclear annihilation once and for all."
Days after Russia's 24 February invasion, President Vladimir Putin put his country's deterrence forces - which include nuclear arms - on high alert, citing what he called aggressive statements by NATO leaders and western economic sanctions against Moscow.
But in a letter to those at the conference, Mr Putin wrote: "There can be no winners in a nuclear war and it should never be unleashed, and we stand for equal and indivisible security for all members of the world community."