The Americans will face the squad from the Communist island nation at Audi Field, home of Major League Soccer's DC United, in the opening game of Group A play in the new CONCACAF (North American) Nations League.
Rankings for the final 2022 World Cup qualifying round will be decided after the event.
The United States are currently ranked 24th in the world, and second in CONCACAF, behind Mexico.
Cuba are 174th, out of 211 FIFA nations, and 22nd in the region. They beat the Turks and Caicos, Grenada and the Dominican Republic in a brief qualifying tournament.
The Americans are 10-1-1 against Cuba in a rivalry dating to 1947 and have won 10 in a row against the Caribbean Lions over the past 70 years, though the teams did not meet for almost 50 years after 1949, in part because the USA severed relations in 1961.