US Secretary of State Antony Blinken began the closed-door talks with the adversaries' foreign ministers at a State Department office just outside Washington, in the second such negotiations session he has led in as many months.
“We continue to believe that peace is within reach and direct dialogue is the key to resolving the remaining issues and reaching a durable and dignified peace,” State Department spokesman Matthew Miller said before the talks, which would cover “very sensitive” areas.
Russia has historically been the mediator between the two former Soviet republics but the US and EU have been increasingly active as Moscow becomes bogged down in its invasion of Ukraine.
Armenia has repeatedly accused Russian peacekeepers of failing to live up to promises to protect ethnic Armenians in line with a 2020 ceasefire negotiated by Moscow after six weeks of fighting left thousands dead.
Russia last week pressed Azerbaijan to allow traffic through the Lachin corridor that links Armenia to Nagorno-Karabakh, a mainly ethnic Armenian area effectively controlled by Yerevan since war during the collapse of the Soviet Union.
The International Committee of the Red Cross said Azerbaijan had blocked access for convoys delivering aid to Karabakh, raising concerns of shortages of food and medicine.
Russia said that Azerbaijan was breaching its obligations to allow traffic to flow.
Azerbaijan has insisted that civilians and aid convoys can travel through, with the blockade since December nominally staged by Azerbaijani activists to protest against illegal mining.