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The last flight out of Cuba departed to Miami at 12:55 p.m., ahead of the April 2 deadline to suspend all flights.
"U.S. citizens in Cuba who normally live in the United States should arrange for immediate return with American Airlines today or be prepared to remain abroad for an indefinite period," the U.S. Embassy in Cuba said in a statement.
The embassy also said that any Americans with future travel plans to Cuba should postpone them until after the coronavirus pandemic is under control.
Cuba is on lockdown until the end of April, and those in the country are advised to quarantine at home. Only Cuban citizens or foreign residents returning home are allowed entry the country but are being monitored by health officials at quarantine centers for two weeks.
Currently, there are 186 confirmed cases of COVID-19 in Cuba, the country's Health Ministry reported on Tuesday. Eight people have died.