US Secretary of State Antony Blinken and Russian Foreign Minister Sergei Lavrov met for talks in Geneva on Friday amid mounting fears that Russia could be about to invade Ukraine.
"This is a critical moment," Mr Blinken said in his opening remarks.
The US and Russia "don't expect to resolve our differences here today", he added, but hoped to test whether diplomacy was still a viable option.
Mr Lavrov said Russia was not expecting a breakthrough in the key talks.
Moscow has 100,000 troops near its borders with Ukraine, but denies planning to invade.
Across the table in a luxury Swiss hotel, Mr Blinken warned his Russian counterpart of a "united, swift and severe" response if Russia did take that step.
President Vladimir Putin has issued demands to the West which he says concern Russia's security, including that Ukraine be stopped from joining Nato.
He wants the Western defensive alliance to abandon military exercises and stop sending weapons to eastern Europe, which Moscow sees as its backyard.
The Kremlin's spokesman said Russia was not expecting a written response to those red lines on Friday. A reply is expected next week, Russian media report.
"[Our] proposals are extremely concrete and we await equally concrete answers," Mr Lavrov said as the talks got under way.
What do the US and Russia want from these talks?
It's very possible that Mr Blinken and Mr Lavrov will emerge with differing accounts of what took place.
State Department officials have said Mr Blinken will seek to offer Mr Lavrov a "diplomatic off-ramp" to ease tensions.
Mr Blinken could offer Russia more transparency on military exercises in the region, or suggest reviving restrictions on missiles in Europe. These rules were previously set out in the Intermediate-Range Nuclear Forces Treaty, a Cold War-era pact that the US scrapped in 2019, after accusing Russia of violating the deal.
Russia maintains that Ukraine is its primary focus. On Thursday it unveiled plans for naval drills involving more than 140 warships and more than 60 aircraft, seen as a show of strength.
The same day, the US warned that Russian intelligence officers had been recruiting current and former Ukrainian government officials to step in as a provisional government and cooperate with an occupying Russian force in the event of an invasion.
The US Treasury Department imposed sanctions on two current Ukrainian members of parliament and two former government officials accused of being part of the plot.
How unified are the US and its allies?
Mr Blinken arrived in Geneva after a trip to Kyiv to show support for Ukraine, and talks with Britain, France and Germany in Berlin.
Several European nations have now moved to bolster Nato's military deployment in eastern Europe. Spain is sending warships to join Nato naval forces in the Mediterranean and the Black Sea, and Denmark also said it would send a frigate to the Baltic Sea.
French President Emmanuel Macron has offered to send troops to Romania.
Earlier this week, Britain announced it was supplying Ukraine with extra troops for training and defensive weapons.
In a speech on Friday, UK Foreign Secretary Liz Truss called on Mr Putin to "desist and step back from Ukraine before he makes a massive strategic mistake" that would lead to terrible loss of life.
President Biden had triggered questions about the consistency of the US line on Ukraine on Wednesday, when he bleakly predicted that Russia "will move in" on Ukraine, but appeared to suggest a "minor incursion" could attract a weaker response from the US and its allies.
The message drew a rebuke from Ukrainian President Volodymyr Zelensky, who tweeted: "There are no minor incursions. Just as there are no minor casualties and little grief from the loss of loved ones."
Mr Biden then sought to clarify by saying any Russian troop movement across Ukraine's border would qualify as an invasion and that Moscow would "pay a heavy price".