The UN-Arab League joint special envoy to Syria, Kofi Annan has announced he is leaving his post.
In a news conference, he said the Syrian people "desperately need action" but criticised the UN Security Council for "finger-pointing and name-calling".
Mr Annan authored a six-point peace plan for Syria which was intended to bring an end to the fighting.
But the plan was never fully adhered to by either side and the violence has continued to escalate.
UN Secretary General Ban Ki-moon said it was "with deep regret" that he announced Mr Annan would not renew his mandate when it expires at the end of August.
The Syrian foreign ministry also expressed regret at the announcement, state TV reported.
Speaking in Geneva, Mr Annan said the increasing militarisation of the Syrian conflict and the "clear lack of unity" in the Security Council had "fundamentally changed the circumstances for the effective exercise of my role".
He said the problems were "compounded by the disunity of the international community".
Russia and China have vetoed resolutions on the crisis three times, citing opposition to any action which might be seen as regime change imposed from outside.
"When the Syrian people desperately need action, there continues to be finger-pointing and name-calling in the Security Council," he said.
"It is impossible for me or anyone to compel the Syrian government, and also the opposition, to take the steps to bring about the political process.
"Syria can still be saved from the worst calamity - if the international community can show the courage and leadership necessary to compromise on their partial interests for the sake of the Syrian people - for the men, women and children who have already suffered far too much."
Mr Annan said he did not rule out someone taking over the mediator's role from him, but said a successor might choose another path.
He said the focus remained on political transition, as President Bashar al-Assad "will have to leave sooner or later".
In his statement, Mr Ban said he was in discussion with the Arab League to find a successor to "carry on this crucial peacemaking effort".
He said Mr Annan deserved "profound admiration" for the way he had tackled "this most difficult and potentially thankless of assignments" and that he remained convinced bloodshed would only bring "deeper suffering to the country and greater peril to the region".
Mr Ban said the Annan plan remained the "best hope for the people of Syria" but that the "persistent divisions" in the UN Security Council "have themselves become an obstacle to diplomacy, making the work of any mediator vastly more difficult".
Speaking in London, Russian President Vladimir Putin said Mr Annan was "a man of great merit, a brilliant diplomat and a very honest person, so it is a great shame".
Russia's UN ambassador, Vitaly Churkin, said Moscow had always supported Mr Annan's work and that it hoped Mr Annan's final month in the role "is going to be used as effectively as possible under these very difficult circumstances".
Writing on Twitter, the US ambassador to the UN, Susan Rice, thanked Mr Annan for his "dedication, service and determined efforts", but said those who had blocked UN resolutions had "made his mission impossible".
White House spokesman Jay Carney blamed Russia and China for the resignation, saying it highlighted their failure at the UN to "support meaningful resolutions against Assad that would have held Assad accountable".
The BBC's Jim Muir, who is monitoring events in Syria from neighbouring Lebanon, said Mr Annan's decision to step down is clear recognition that the political process has failed, and that Syria's fate will be decided by events on the ground.
It is hard to imagine a figure with anything approaching the stature and profile of Mr Annan taking over the task, when the prospects for success are currently negligible, our correspondent adds.
Mr Annan took up his post in February. His internationally backed peace plan called for an end to the use of heavy weaponry, the free passage of aid, freedom of media and demonstration and for a Syrian-led political process to address the aspirations and concerns of the Syrian people.
It was supposed to come into effect in mid-April, but government forces continued to shell opposition strongholds and the opposition forces never fully committed to it.
Activists estimate some 20,000 people have died since anti-government protests erupted against President Assad in March last year. Tens of thousands of people have also fled the country.
On Thursday, rebel fighters in Syria's second city, Aleppo, attacked an army base using a tank they had seized from the military.
In the capital, Damascus, government forces launched two operations to root out rebel activists on Wednesday, killing at least 70, the opposition said.