February, on what is one of his most diplomatically delicate missions to date.
The visit coincides with the first anniversary of Putin's return to the Kremlin for a historic third term on May 7, 2012 which heralded a new chill in relations between Moscow and Washington.
Syria is likely to top the agenda when the two men meet later on Tuesday with the 26-month war threatening to spill across the region. Later, Kerry will also meet foreign minister Sergei Lavrov.
Washington has long urged Moscow - Syrian President Bashar al-Assad's most powerful ally - to use its sway to halt the bloodshed, accusing Russian leaders of continuing to arm the Syrian regime.
And while Moscow has insisted on the need for a political solution to the fighting it has grown increasingly alarmed by the war. The foreign ministry said it was "especially" concerned by Israeli strikes on Syrian targets, warning the violence threatens neighbouring Lebanon.
There are a host of other issues on the agenda of the talks, including last month's Boston marathon bombings blamed on two brothers of Chechen descent.
More contentious dossiers include American missile defence, and rows over a ban by Moscow on American adoptions of Russian children and the Russian authorities' harassment of NGOs.
"Our counterparts here have made clear they are ready to engage on Syria, but they have many issues that they want to talk about," a senior State Department official said Monday.
He acknowledged it was not often American officials managed to hold direct talks with Putin, describing Tuesday's meeting as "a fantastic opportunity" for talks on the entire bilateral relationship.
With events moving on the ground in Syria, it "is a time to talk to the Russians to understand that from our side we remain committed (to a political solution), and if they are as well then we need to think about how to work operationally to make that happen," a second top US official said.
"I don't know if we will get an agreement or not, but we certainly think it is worth testing and trying to find some ways forward."
Stepped up cooperation on counter-terrorism would also be high on the agenda for the talks, following the Boston bombings.
With Putin marking a year to the day since he was inaugurated for a third term as president after disputed elections, the visit also comes amid renewed protests against his rule.
On Monday, thousands of protestors filled a Moscow square to denounce Putin and revive the momentum of the protest movement which has faltered in the last months.
"Putin is a thief," charismatic opposition figurehead Alexei Navalny said to cheers from the crowds on Monday. "We will throw him out of the Kremlin."
Kerry is due to meet civil society activists on Wednesday at the residence of Ambassador Michael McFaul at which he will hear their concerns about the lack of democratic progress.
Washington has called for a more open and democratic society, angering Putin and leading him to accuse American-supported non-governmental organisations of actively working against him.