Guterres spoke to reporters to mark the start of his 10th and final year in office. The UN Security Council will choose his successor later in 2026.
"Global problems will not be solved by one power calling the shots," said Guterres, later adding it was a reference to the US.
"Nor will they be solved by two powers carving the world into rival spheres of influence."
When asked to clarify, he said many see a future in which there are two poles, one centred in the US and one in China.
"If we want a stable world, if we want a world in which peace can be sustained, in which development can be generalised, and in which - in the end - our values will prevail, we need to support multipolarity."
The US and Chinese missions to the United Nations did not immediately respond to a request for comment.
US President Donald Trump, who began his second term a year ago, is resuscitating what much of the international community had long spurned as an outdated worldview - spheres of influence carved out by the big powers.
He has vowed to restore US dominance in the Western hemisphere.
Guterres' remarks come a week after Trump launched his Board of Peace. This was initially designed to cement Gaza's rocky ceasefire, but Trump foresees it taking a wider role, an approach that worries some global powers.
"In my opinion, the basic responsibility for international peace and security lies with the UN, lies with the Security Council," Guterres said.
"That is the reason why it is so important to reform the Security Council. And it's very interesting to see that some that criticise the UN for being not effective are the ones opposing the reform of the Security Council.
"That is the reason why the UN can sometimes not be as effective as we all want."
Guterres' second five-year term has been marked by Russia's full-scale invasion of Ukraine, the return of the Taliban in Afghanistan, the conflict in Sudan, the war between Israel and Palestinian militants Hamas in the Gaza Strip, a rapid end to Syria's civil war and the US capture of Venezuela's President Nicolas Maduro.
"International law is trampled. Co-operation is eroding. And multilateral institutions are under assault on many fronts," said Guterres.
"Impunity is driving today's conflicts – fuelling escalation, widening mistrust, and kicking the doors open for powerful spoilers to enter from every direction."
The UN is facing a cash crisis as the world body's largest contributor - the United States - has slashed voluntary funding to UN agencies and refused to make mandatory payments to the UN's regular and peacekeeping budgets.
He launched a reform task force in March, known as UN80, which seeks to cut costs and improve efficiency.
