Kerry's talks in Geneva with Foreign Minister Sergei Lavrov, which officials said could last until Saturday, mark a significant shift in the world's response to the war in Syria.
Just as Kerry was leaving, envoys from the five permanent members of the UN Security Council held a first inconclusive meeting on Russia's plan to secure Syria's banned arms.
US President Barack Obama, who on Tuesday set aside a threatened military strike against Bashar al-Assad's government, has said Moscow's plan could be a "significant breakthrough."
But before Washington can give its full backing, US officials said, Kerry must meet Lavrov and test how serious Russia is about destroying the arsenal.
Backed by a team of arms experts, Kerry will spend two to three days in Geneva poring over the details of Russia's proposal.
This week's surprise diplomatic opening came after Kerry, in a seemingly off-the-cuff remark, said Assad could avert US military action if he handed over the alleged weapons.
The opening was speedily embraced by Russia, which has already passed to Washington what the State Department called "ideas" containing "a number of components and details."
"Secretary Kerry and Foreign Minister Lavrov spoke this morning in advance of the meeting in Geneva tomorrow," a senior State Department official told reporters.
"They discussed the outlines of the schedule and their shared objective of having a substantive discussion about the mechanics of identifying, verifying and ultimately destroying Assad's chemical weapons stockpile so they can never be used again."
In Geneva, US arms experts will seek to hammer out with the Russians a mechanism by which the weapons could be secured and then destroyed under international supervisions.
Lavrov said earlier that it would be "unacceptable" for the Security Council to pass a text to authorize enforcement action against Syria.
At Russia's urging, Damascus has said it wants to put its arsenal of chemical weapons under international supervision in compliance with the 1993 convention banning the weapons.
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