The United States established diplomatic relations with Uganda in 1962, following Uganda’s formal independence from the United Kingdom. In the post-independence period, the country endured despotism and near economic collapse. The human rights abuses of several Ugandan governments strained U.S. relations with Uganda. President Museveni came to power in 1986, after decades of internal strife. Under Museveni, Uganda has experienced relative political stability, democratic progress, and economic growth.

The country has made strides in reducing HIV/AIDS, experienced economic growth, and stabilized its north, where the Lord's Resistance Army (LRA) operated for 20 years. Uganda faces numerous challenges, however, including population growth, power and infrastructure constraints, corruption, underdeveloped democratic institutions, and human rights deficits. Uganda is a key U.S. strategic partner, particularly through its contribution to the African Union Mission in Somalia. In addition, Uganda and other governments of the region, under the leadership of the African Union and with the support of the United States, have made progress in weakening the LRA and reducing its threat to central Africa.