Modern diplomatic relations between Cuba and the United States are cold, stemming from historic conflict and divergent political ideologies. The two nations restored diplomatic relations on July 20, 2015, after relations had been severed in 1961 during the Cold War. The U.S. has maintained a comprehensive trade embargo against Cuba since 1960. The embargo includes restrictions on all commercial, economic, and financial activity, making it illegal for U.S. corporations to do business with Cuba.

Early 19th century relations centered mainly on extensive trade, before manifest destiny increasingly led to an American desire to buy, conquer, or control Cuba. The U.S. attempted to purchase Cuba in 1848 and in 1854 from Spain. It successfully took over Cuba in 1898 as a U.S. territory within the Treaty of Paris. The U.S. position of economic and political dominance over the island persisted after Cuba became formally independent in 1902. Relations became closer still as the U.S. provided weapons, money, and its authority to the military dictatorship of Fulgencio Batista that ruled Cuba from 1952 to 1958. They deteriorated during the Cuban Revolution of 1959. The U.S. recruited operatives in Cuba to carry out a violent campaign of terrorism and sabotage on the island, killing civilians and causing economic damage.

The U.S. government terrorism campaign against Cuba was accelerated from early 1960. Later that year Cuba nationalized all U.S-owned on-shore oil refineries, seizing approximately $1.7 billion in U.S. oil assets. In 1961, the U.S. severed diplomatic ties with Cuba and attempted to invade the country; following its failure the U.S. engaged in a violent campaign of terrorist attacks to overthrow the Cuban government, killing a significant number of civilians. A year later, during the Cuban Missile Crisis, Cuba permitted the Soviet Union to deploy nuclear missiles on the island, which led the U.S. government to blockade the island.

Relations briefly normalized from 2015 to 2017, under U.S. President Barack Obama and First Secretary of the Communist Party of Cuba Raúl Castro, in an effort known as the Cuban thaw. Relations have since materially deteriorated due to stark differences on immigration, counterterrorism, civil and political rights, human rights, electoral interference, disinformation campaigns, humanitarian aid, trade policy, financial claims, fugitive extradition and Cuban foreign policy. The U.S. designated Cuba a state sponsor of terrorism three times: from 1982 to 2015, 2021 to 2025, and since 2025. U.S. representation in Cuba is handled by the United States Embassy in Havana, and there is a similar Cuban Embassy in Washington, D.C.

Relations between the Spanish colony of Cuba and polities on the North American mainland first established themselves in the early 18th century through illicit commercial contracts by the European colonies of the New World, trading to elude colonial taxes. As both legal and illegal trade increased, Cuba became a comparatively prosperous trading partner in the region, and a center of tobacco and sugar production. During this period Cuban merchants increasingly traveled to North American ports, establishing trade contracts that endured for many years.

The British capture and temporary occupation of Havana in 1762, which many Americans participated in, opened up trade with the colonies in North and South America, and the American Revolution in 1776 provided additional trade opportunities. Spain opened Cuban ports to North American commerce officially in November 1776 and the island became increasingly dependent on that trade.

After the opening of the island to world trade in 1818, trade agreements began to replace Spanish commercial connections. In 1820 Thomas Jefferson thought Cuba is "the most interesting addition which could ever be made to our system of States" and told Secretary of War John C. Calhoun that the United States "ought, at the first possible opportunity, to take Cuba." In a letter to the U.S. Minister to Spain Hugh Nelson, Secretary of State John Quincy Adams described the likelihood of U.S. "annexation of Cuba" within half a century despite obstacles: "But there are laws of political as well as of physical gravitation; and if an apple severed by the tempest from its native tree cannot choose but fall to the ground, Cuba, forcibly disjoined from its own unnatural connection with Spain, and incapable of self support, can gravitate only towards the North American Union, which by the same law of nature cannot cast her off from its bosom."

The desire to procure Cuba intensified in the 1840s, not only in the context of manifest destiny but also in the interest of Southern power. Cuba, with some half a million slaves, would provide Southerners with extra leverage in Congress. In the late 1840s, President James K. Polk dispatched his minister to Spain Romulus Mitchell Saunders with a mission to offer $100 million to buy Cuba. Saunders however did not speak Spanish, and as then Secretary of State James Buchanan noted "even [English] he sometimes murders". Saunders was a clumsy negotiator, which both entertained and angered the Spanish. Spain replied that they would "prefer seeing [Cuba] sunk in the ocean" than sold. It may have been a moot point anyway, as it is unlikely that the Whig majority House would have accepted such an obviously pro-Southern move. The 1848 election of Zachary Taylor, a Whig, ended formal attempts to purchase the island.