The article examines in a broad historical context the key features of the US policy on the Nagorno-Karabakh conflict settlement and normalization of relations between Armenia and Azerbaijan. Two main periods of evolution of this policy are emphasized: the first – from the early 1990s to 2020, the second – from 2020 to the present. It is noted that in periods of insreasing military and political instability in the region, the U.S. seeks to use the Karabakh settlement and development of relations with Armenia and Azerbaijan to reduce Russia's influence in the South Caucasus.