The political relationship between the United States of America and Myanmar began to face major problems following the 1988 military coup and the junta's outbursts of repression against pro-democracy activists.

[7] The first contact between the Konbaung Dynasty of Burma and the United States were the letters sent from King Mindon in 1856–57 to Presidents Franklin Pierce and James Buchanan.

[11]: 65–66 In response to Prime Minister U Nu's policies of moderate socialism in the 1950s,[12]: 217  the United States Embassy in Rangoon translated and published George Orwell's Animal Farm in Burmese, as a propaganda tool.

[20] The United States downgraded its level of representation in Myanmar from Ambassador to Chargé d'Affaires after the government's crackdown on the democratic opposition in 1988 and its failure to honour the results of the 1990 parliamentary election.

A number of U.S. companies exited the Myanmar market even prior to the imposition of sanctions due to a worsening business climate and mounting criticism from human rights groups, consumers, and shareholders.

[citation needed] Later, the United States federal government imposed broad sanctions against Myanmar under several different legislative and policy vehicles.

The BFDA was accompanied by Executive Order 13310 banning the import of products and export of financial services to Myanmar signed in the aftermath of the Depayin massacre.

In response, the U.S. Department of Treasury designated 25 senior Burmese government officials as subject to an asset block under Executive Order 13310 on 27 September 2007.

13448) expanding the authority to block assets to individuals who are responsible for human rights abuses and public corruption, as well as those who provide material and financial support to the regime.

[3] On January 13, 2012, the US Secretary of State Hillary Clinton announced the US will exchange ambassadors with Myanmar, after a landmark Burmese political prisoner amnesty.

[27][28] After being confirmed by the U.S. Senate in late June, Derek Mitchell, the first U.S. ambassador to Myanmar in 22 years formally assumed his job on July 11, 2012, by presenting his credentials to President Thein Sein at the presidential mansion in the capital Naypyidaw.

[31] Secretary of State Hillary Clinton announced plans in the spring of 2012 for a “targeted easing” of sanctions to allow American dollars to enter the country.

[31] President Obama ordered the U.S. Treasury Department to issue two licenses, one giving special permission for investment in Myanmar and the other allowing financial services.

[32] President Obama also issued an executive order expanding existing sanctions against individuals to include those who threaten Myanmar's political restructuring process.

Businesses with more than $500,000 in investment in the country were required to file an annual report with the State Department, with details on workers’ rights, land acquisitions and any payments of more than $10,000 to government entities and state-owned enterprises.

[34] American companies and people were allowed to invest in the state-owned Myanmar Oil and Gas Enterprise leading to criticism by human rights groups.

HRW's director Arvind Ganesan said that it looked as if the U.S. had caved to industry pressure undercutting Aung San Suu Kyi and others promoting accountability in the reformed military government.

[29] After the NLD's historic election win in 2015 with a transfer of power, the new government led by Aung San Suu Kyi enjoyed friendlier relations with the U.S.

[37] The United States did not immediately re-impose sanctions on Myanmar as a response to this, which was met with criticism by Congressional lawmakers and human rights activists.

[39] In August 2018, the United States Treasury Department enacted these economic sanctions on four Myanmar military and police commanders in a statement, referring to the violence against the Rohingya as “ethnic cleansing.” Those targeted by this sanction are: Aung Kyaw Zaw, Khin Maung Soe, Khin Hlaing, Thura San Lwin, as well as the Burmese Army's 33rd Light Infantry Division, and the 99th Light Infantry Division.

[47] The G7 nations, including the United States, issued a joint statement condemning the executions for its disregard of human rights and the rule of law.

[51][52] On October 26, 2023, at the State Administration Council meeting, General Min Aung Hlaing blamed the US for its containment policy against China and provoking unrest in Myanmar.

[59] According to WikiLeaks cables, the United States funded some of the civil society groups in Myanmar that forced the government to suspend a controversial Chinese Myitsone Dam on the Irrawaddy river.