The U.S. Embassy suspended operations in Bissau on June 14, 1998, in the midst of violent conflict between forces loyal to then-President Vieira and the military-led junta.

Prior to and following the embassy closure, the United States and Guinea-Bissau had enjoyed excellent bilateral relations.

The United States and Guinea-Bissau signed an international military education and training (IMET) agreement in 1986, and prior to 1998, the U.S. provided English-language teaching facilities as well as communications and navigational equipment to support the navy's coastal surveillance program.

In August 2004, sanctions under Section 508 of the Foreign Operations Appropriations Act—which were imposed as a result of the September 2003 military coup—were lifted and Bissau once again became eligible for IMET and other direct aid.

In March 2007, the U.S. and Brazil signed a Tripartite Memorandum of Understanding with Guinea-Bissau highlighting a parliamentary strengthening project first implemented in 2005.