Secretary of State John Kerry is meeting Russian Foreign Minister Sergei Lavrov for the first time since he accused Russia of lying about its role in Ukraine’s war.
The talks in Geneva coincide with a UN report on human rights violations and the humanitarian crisis in east Ukraine.
The UN says the conflict has claimed at least 6,000 lives, with hundreds killed in the past few weeks alone.
A fragile ceasefire is holding despite some fighting in recent days.
At his meeting in Geneva, John Kerry is also expected to raise the brutal murder of Russian opposition politician Boris Nemtsov in Moscow on February 27.
Boris Nemtsov, who was shot on a bridge near the Kremlin, had been planning an anti-war rally and was said to be working on a report to expose the presence of Russian troops in Ukraine.
John Kerry will press for an investigation that he said should examine not only who pulled the trigger, but who ordered, funded and co-ordinated Boris Nemtsov’s murder.
Separately, John Kerry is also expected to renew negotiations with Iran’s Foreign Minister, Mohammad Javad Zarif, on Tehran’s nuclear program.
There is an end of March deadline to reach agreement on limiting the program, in return for an easing of economic sanctions on Iran.
The talks on Ukraine are expected to be tense after John Kerry last week accused Russian officials of lying to him about Moscow’s support for rebels in eastern Ukraine.
During a visit to London on February 21, John Kerry accused the Kremlin of “craven behavior” in its support for the rebels in east Ukraine, undermining a ceasefire.
Fighting began in Ukraine’s eastern Donetsk and Luhansk regions last April, a month after Russia annexed the Crimea peninsula.
The UN estimates that at least 1.25 million have fled their homes, and believes that the real number of fatalities could be considerably higher than the 6,000 it has given.
In its latest report, released on March 2, it refers to credible accounts of heavy weapons and foreign fighters continuing to flow into eastern Ukraine from Russia.
The Ukrainian government, Western leaders and NATO say there is clear evidence that Russia is helping the rebels with heavy weapons and soldiers.
Independent experts echo that accusation but Moscow denies it, insisting that any Russians serving with the rebels are “volunteers”.
Both sides in the conflict have been pulling back some heavy weaponry from the front line – one of the conditions of the ceasefire agreement signed in the Belarusian capital Minsk last month.
Monitors from the OSCE security group have reported weapons movements on both sides but say it is too early to confirm a full withdrawal. Meanwhile violence continued over the weekend.