The UN chief was laying out his priorities in a speech to the General Assembly for the year ahead, at a time when the organization faces unprecedented crises and polarization.
"Our actions -- or inactions -- have unleashed a modern-day Pandora's box of ills," Guterres said.
"Four of those ills stand out because they represent, at best, threats that could disrupt every aspect of our agenda and, at worst, upend our very existence: Runaway conflicts. Rampant inequalities. The raging climate crisis. And out-of-control technology."
Guterres's organization is facing some of the worst crises in its history.
The organization's top decision-making body, the Security Council, is paralyzed. The war in Gaza has seen Israel and its allies attack the UN's neutrality, and blue helmet peacekeepers have been caught in the crossfire in Lebanon and Syria.
- 'Our tumultuous world' -
The return of US President-elect Donald Trump to the White House could further complicate Guterres's agenda, experts have warned.
"Yes, there is progress in our tumultuous world," Guterres said, pointing to the relative success of the ceasefire in Lebanon and the pace of renewable energy development.
"But let's have no illusions: This is very much a world in turmoil and grave uncertainty."
"Conflicts are multiplying, becoming messier and deadlier. Deepening geo-political divisions and mistrust are adding fuel to the fire. The nuclear threat is at its highest in decades," he said.
As conflict rages in Sudan and Gaza, Guterres said "the spectrum of human rights is under constant attack. Impunity is endemic -- with serial violations of international law, international humanitarian law and the UN Charter -- and systematic assaults on our very institutions."
As efforts to broker a ceasefire between Hamas and Israel in Gaza appear to be closing in on a breakthrough, Guterres reiterated his call for a durable ceasefire.
"I strongly appeal to all parties to finalize a ceasefire and hostage release deal," he said.
He also expressed concern about the ongoing reorganization of the Middle East -- from Iran to Syria -- and what it could lead to.
"Across the region, we are seeing a reshaping of the Middle East. What is far less clear is what will emerge," he said.
The UN boss, who for years has made the fight against global warming one of his priorities, again denounced fossil fuel companies "ravaging and savaging our world.
"Look no further than the hills of Los Angeles. It has gone from the home of disaster movies to a scene of disaster," he said.
Guterres also announced a new climate change conference, expected to be held ahead of the next COP climate talks in Belem.
"We will convene a special event to take stock of the plans of all countries, push for action to keep 1.5 (degrees Celsius warming over pre-industrial levels) within reach, and deliver climate justice."
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