"This morning, in light of what is at stake in these talks, I appeal to both sides to make the most of this moment," he said, in an online statement broadcast from Washington.
While the top US diplomat aimed his remarks at both sides, his message was clearly directed at the opposition, which has threatened to leave Geneva even before talks start.
The opposition High Negotiations Committee has demanded that humanitarian aid be allowed to flow to besieged towns before even engaging in indirect talks with Assad's envoys.
"The town of Madaya is just an hour's drive from Damascus and yet its people have been reduced to eating grass and leaves," Kerry said.
"How have the regime and the militias that support it responded? By planting landmines and erecting barbed wire to keep relief workers out," he said.
Kerry said Washington had received credible reports that another 16 people had starved to death in the rebel-held, regime-besieged community over the weekend.
But he described the opening of talks in Geneva under UN envoy Staffan de Mistura as a "pivotal phase" and described the HNC as representing an "inclusive opposition."
"The world is hoping both sides will move quickly to meet the needs of millions of desperate Syrians," he added.
And he warned that if ceasefire talks fail the war will destroy what is left of Syria and leave the field open to recruiters from the Islamic State jihadist group.
"Now, while battlefield dynamics can effect negotiating leverage, in the end there is no military solution to the conflict," he argued.
"Without negotiations the bloodshed will drag on until the last city is reduced to rubble ... And that will ensure an increased number of terrorists, created by and attracted to this fight."
But he has so far made no plans to join the negotiating parties there, preferring to leave the "proximity talks" under the auspices De Mistura and the United Nations.
Instead, he was to fly out of Washington later Sunday to Rome and a meeting of the core countries of the US-led military coalition fighting the IS group.
And later in the week he is due in London for a conference of donors to the humanitarian effort in Syria.
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