The army has taken control of the last supply route linking opposition forces to Turkey.
Syrian government forces cut rebel supply lines to Aleppo under cover of Russian air power on Wednesday, in what could be a pivotal moment in the five-year war.
After three days of intense fighting and aerial bombardment, regime forces, believed to include Iran-backed Shia militias, broke through to the formerly besieged regime enclaves of Nobul and Zahra.
In so doing, they cut rebel-held eastern Aleppo off from outside help. With regime forces to the south and west and Islamic State of Iraq and the Levant to the east, the part held by non-Isil rebels is now surrounded.
By nightfall, rebel forces were mounting a final stand from a mile-long patch of territory north-east of Aleppo. But local media activists aid the opposition forces were on the verge of withdrawal, facing massive bombardment from Russian and regime air strikes.
Aleppo is Syria's largest city, and its eventual capture by the regime would almost mark a decisive fight-back. Both rebels and outside analysts say that is still a long way off, but the imposition of a siege would be an important moment.
Medics rushed to stockpile supplies as civilian and military casualties poured in. “We are gathering everything we have,” said one doctor. “I have seen injuries like you cannot believe.”
Russia and the regime were bombing “everything”, said Abu Alez, another doctor, speaking from a clinic that had treated more than 100 injured civilians.
The United Nations said three aid workers had been killed and hundreds of families displaced in towns around the city, following an “unprecedented frequency” of airstrikes in the past two days.
Five months into Russia’s military intervention in Syria, rebel forces are buckling on three fronts while the West tries to push them to the negotiating table and end the war.
Rebels in the north-eastern province of Latakia, where the regime and its backers have focused most of their resources, have also been ground down and pushed out of their final strongholds. They are under intense pressure in the south between Damascus and the Jordanian border.
The assault on Aleppo and several other fronts has provoked fury amongst opposition delegates attending peace talks in Geneva, who accused Moscow and Damascus of using force to wring concessions from them at the negotiating table.
"Russia is using the political process as a cover to impose its military solution on the ground," Salem al-Meslet, a member of High Negotiations Committee, the main opposition delegation, told Reuters on Wednesday.
On Wednesday, the UN special envoy for Syria, Staffan de Mistura, announced a "temporary pause" in the process, saying the troubled talks would be postponed for three weeks.