Early 19th century relations centered mainly on extensive trade, before manifest destiny increasingly led to an American desire to buy, conquer, or control Cuba.

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.

"[18] 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.

[20] In August 1851, 40 Americans who took part in Narciso López's filibustering Lopez Expedition in Cuba, including the Attorney General's nephew William L. Crittenden, were executed by Spanish authorities in Havana.

Between 1878 and 1898 American investors took advantage of deteriorating economic conditions of the Ten Years' War to take over estates they had tried unsuccessfully to buy before while others acquired properties at very low prices.

U.S. Secretary of State James G. Blaine wrote in 1881 of Cuba, "that rich island, the key to the Gulf of Mexico, and the field for our most extended trade in the Western Hemisphere, is, though in the hands of Spain, a part of the American commercial system ...

The Platt Amendment defined the terms of Cuban-U.S. relations for the following 33 years and provided the legal basis for U.S. military interventions with varying degrees of support from Cuban governments and political parties.

[citation needed] Despite recognizing Cuba's transition into an independent republic, United States Governor Charles Edward Magoon assumed temporary military rule for three more years following a rebellion led in part by José Miguel Gómez.

President Franklin D. Roosevelt, despite his promotion of the Good Neighbor policy toward Latin America, ordered 29 warships to Cuba and Key West, alerting United States Marines, and bombers for use if necessary.

On 4 September 1959, Ambassador Bonsal met with Cuban Premier Fidel Castro to express "serious concern at the treatment being given to American private interests in Cuba both agriculture and utilities.

[41] That same month, President Eisenhower quietly authorized the Central Intelligence Agency (CIA) to organize, train, and equip Cuban refugees as a guerrilla force to overthrow Castro.

Later that year, U.S. diplomats Edwin L. Sweet and William G. Friedman were arrested and expelled from the island having been charged with "encouraging terrorist acts, granting asylum, financing subversive publications and smuggling weapons".

He criticized what he saw as use of U.S. government influence to advance the interest and increase the profits of private U.S. companies instead of helping Cuba to achieve economic progress, saying that Americans dominated the island's economy and had given support to one of the bloodiest and most repressive dictatorships in the history of Latin America.

[citation needed] A U.S. Senate Select Intelligence Committee report later confirmed over eight attempted plots to kill Castro between 1960 and 1965, as well as additional plans against other Cuban leaders.

[citation needed] Beginning in the 1970s a growing and coordinated effort by US-based Cuban dissident groups organized to confront the Castro regime through international bodies such as the United Nations.

In a statement to the Senate, Weinmann explained that the organization is "a national group of prominent Americans who advocate normal trade of food and medical products between the United States and Cuba."

Its most prominent members included David Rockefeller, Milton Friedman, Carla Hills, Frank Carlucci, John Whitehead, Paul Volcker, Julius Richmond, Craig L. Fuller, Sam Gibbons, James Rodney Schlesinger, among others.

Tensions heightened as the Under Secretary of State for Arms Control and International Security Affairs, John R. Bolton, accused Cuba of maintaining a biological weapons program.

[68][69] Bolton identified the Castro government as part of America's "axis of evil", highlighting the fact that the Cuban leader visited several U.S. foes, including Libya, Iran and Syria.

[citation needed] In January 2006, United States Interests Section in Havana began, in an attempt to break Cuba's "information blockade", displaying messages, including quotes from the Universal Declaration of Human Rights, on a scrolling "electronic billboard" in the windows of their top floor.

The commission immediately announced a series of measures that included a tightening of the travel embargo to the island, a crackdown on illegal cash transfers, and a more robust information campaign aimed at Cuba.

[67] In April 2006, the Bush administration appointed Caleb McCarry "transition coordinator" for Cuba, providing a budget of $59 million, with the task of promoting the governmental shift to democracy after Castro's death.

The report included a plan that suggested the United States spend $80 million to ensure that Cuba's communist system did not outlive the death of Fidel Castro.

The plan also featured a classified annex that Cuban officials mistakenly claimed could be a plot to assassinate Fidel Castro or a United States military invasion of Cuba.

[89] Beginning in 2013, Cuban and U.S. officials held secret talks brokered in part by Pope Francis and hosted in Canada and Vatican City[90][91][92] to start the process of restoring diplomatic relations between Cuba and the United States.

[128][129] On September 19th, 2019, the Canadian Broadcasting Corporation's Fifth Estate news organization posted an article indicating that "Havana Syndrome" may have been caused by accidental exposure to neurotoxic agents.

[135] In June 2021, the Biden administration continued America's tradition of voting against an annual United Nations General Assembly resolution calling for an end to the U.S. economic embargo against Cuba.

[138] The Biden administration sanctioned a key Cuban official and a government special forces unit known as the Boinas Negras for human rights abuses in the wake of historic protests on the island.

"[141] President Biden has also ordered government specialists to develop ideas for the U.S. to unilaterally extend internet access on the island, and he has promised to enhance backing for Cuban dissidents.

[142] In December 2021, 114 Democratic House members signed a letter that urged President Biden to lift restrictions and sanctions against Cuba in order to make their access to food and medicine easier.