Russia and the US disagreed sharply over the chaos in Syria, with Barack Obama urging a political transition to replace its president but Vladimir Putin warning it would be a mistake to abandon Bashar Assad.
After both speaking at the United Nations General Assembly, Mr Obama and Mr Putin also met privately for 90 minutes - their first face-to-face encounter in nearly a year.
At the heart of their dispute over Syria is the fate of Assad, the embattled Syrian leader who is a Russian ally.
The US has long called for him to leave power, while Russia has cast the Syrian government as the only viable option for confronting Islamic State, the militant group that has taken advantage of the vacuum created by the civil war.
During his address to the UN, Mr Obama declared: "We must recognise that there cannot be, after so much bloodshed, so much carnage, a return to the pre-war status quo."
Mr Putin, speaking shortly after the US president, urged the world to stick with Assad.
"We believe it's a huge mistake to refuse to co-operate with the Syrian authorities, with the government forces, those who are bravely fighting terror face-to-face," Mr Putin said during his first appearance at the UN gathering in a decade.
Mr Obama and Mr Putin's differing views of the grim situation in Syria left little indication of how the two countries might work together to end a conflict that has killed more than 250,000 people and resulted in a flood of refugees.
Indeed, the leaders' private meetings ended with vague statements about the need for a political resolution to the crisis, but no clear pathway for making that happen.
The crisis has taken on fresh urgency amid Russia's recent military build-up in Syria.
Mr Putin has cast the increased presence of equipment and troops in Syria as part of the effort to defeat IS, and has suggested that Russia could launch airstrikes against the militants.
"We are thinking about it and don't exclude anything," he said.
It is unlikely Mr Putin would join the US-led coalition already launching strikes against the militants.
He said Russia will only take such a step in accordance with international law, and criticised the US and its allies for striking the Syrian territory without UN permission.
The Syria crisis largely overshadowed the summit's other discussions on peacekeeping, climate change and global poverty.
French president Francois Hollande backed Mr Obama's call for Assad to be ousted, saying "nobody can imagine" a political solution in Syria if he is still in power.
Mr Hollande called on countries with influence in Syria, including Gulf nations and Iran, to be engaged in a transition.
However, Iran - which along with Russia is a strong backer of Assad - said the Syrian president must remain in power to fight extremists.
Iranian president Hasan Rouhani said that while Syria's government needs reform, the country will fall to IS if the international community makes getting rid of Assad its top goal.
Mr Obama and Mr Putin briefly shook hands during a leaders' lunch that followed the morning of speeches. Seated at the same table, they clinked glasses during a toast, with Mr Putin smiling and Mr Obama grim-faced.
The leaders have long had a strained relationship, with ties deteriorating to post-Cold War lows after Russia annexed Crimea from Ukraine and allegedly backed rebels in Ukraine's east. The US has sought to punish Russia through economic sanctions.
US officials said the situation in Ukraine consumed about half of the meeting. The White House is worried pro-Russian separatists in eastern Ukraine could hold local elections next month that violate a fragile peace plan, and Mr Obama urged Mr Putin to help keep the accord on track.
The peace deal was brokered in February by France and Germany, and Russia does not want the US to become engaged in those talks.
Mr Putin, however, sought to downplay any differences with the US on Ukraine following his meeting with Mr Obama, saying that Washington was working with the Ukrainians and the Europeans to maintain diplomatic contacts with Russia to help with a settlement.