In a strongly worded speech after a meeting of foreign ministers in Paris, Kerry said the Syrian government and Russia must provide guarantees to opposition fighters in Aleppo that they won't be "marching into a massacre" if there is a ceasefire.
The Paris meeting came ahead of talks in Geneva, Switzerland, between US and Russian officials on the situation in Aleppo, where an estimated 100,000 people are trapped
in dire conditions in a shrinking rebel-held area as Syrian regime forces advance.
Speaking alongside the foreign ministers of France, Germany and Qatar, Kerry said civilians must be given safe passage out of Aleppo and humanitarian aid allowed in.
He said there "could be a way forward" but it would depend on the Syrian regime and its powerful backer, Russia, giving rebel fighters confidence they could leave Aleppo safely.
"The choice for many of them as they think about it today is: Die in Aleppo or die in Idlib, but die. That's the way they see the choice," he said of the opposition forces.
"And it seems to me that the (Syrian) regime and Russia have a fundamental responsibility here that if they are trying to effect a genuine transition ... and a genuine cessation of hostilities to permit people to move, they need to provide guarantees and allow guarantees to be put in place that make certain that people are not marching into a massacre."
Kerry: 'Show a little grace'
Kerry urged both Russia and the regime to "show a little grace" to find a mediated solution, warning that if Aleppo were to fall, it would not mean an end to the war but would risk emboldening extremist forces in the country.
The secretary of state also warned the Syrian regime was committing war crimes in its bombardment of eastern Aleppo.
"The indiscriminate bombing by the regime which violates international rules of war -- in many cases crimes, crimes against humanity, and war crimes -- needs to stop," he said.
"And those who support it -- those in Moscow and elsewhere -- should do their utmost to bring it to a close. A meaningful ceasefire needs to be reached."
Syrian President Bashar al-Assad views all opposition fighters as "terrorists," a stance that Russia shares.
Germany: No giving up on humanitarian aid
German Foreign Minister Frank-Walter Steinmeier said he was "speechless" over the worsening situation in Aleppo.
"There are no words to describe the suffering in Aleppo and the absolute destruction of the city. The first priority must be to limit the suffering of these people," he said. "We have attempted several times to deliver aid to the people in Aleppo and it has failed. But that doesn't mean we can afford to give up."
Steinmeier highlighted the plight of the Syria Civil Defense, or White Helmets, whose volunteers continue to rescue those caught up in bombings despite great risk.
And he stressed that the presence of extremist groups in Aleppo doesn't justify the "total destruction" of a city by those fighting them.
"Even if Aleppo falls other fighting will keep happening in Syria," he said. "We will have to hold people accountable. People who are guilty of war crimes. We will do everything to put an end to this and find a political solution."
UK Foreign Secretary Boris Johnson, who was also at the meeting in Paris, said it was essential that the Syrian regime and its backers give the United Nations access to provide humanitarian aid in Aleppo.
"There can be no military solution in Syria," he added. "We must keep pushing for a return to a political process with the credibility necessary for all parties to commit to an end to all the fighting."
Western Aleppo shelled
Tens of people were killed from Friday evening into Saturday in government-controlled Aleppo, according to the UK-based Syrian Observatory for Human Rights monitoring group and the state-run Syrian news agency SANA.
Twenty-five people have been killed and dozens more wounded after rebels fired mortar rounds at neighborhoods in regime-held areas of western Aleppo since Friday evening, the monitoring group said.
SANA, meanwhile, reported that 20 were killed and 165 wounded Friday and Saturday in the apparent rebel shelling of western Aleppo.
There are no numbers yet for how many have been killed Saturday in shelling and strikes on remaining rebel-held areas in eastern Aleppo.