The US and Madagascar have been partners in development for over 30 years. U.S. assistance to Madagascar dates back to the early 1960s, consisting mostly of emergency food aid, loans and grants.

The USAID Madagascar field office was officially opened in September 1984 to support policy reform, economic stabilization, and rehabilitation efforts underway at the time. Initial assistance provided during the four year period of 1984-1988 prioritized investment in the rice sector to increase agricultural production and emergency food aid. In the 1990s, greater attention was paid to Madagascar's unique biodiversity. Consequently, the USAID biodiversity and environmental conservation program was initiated during this period with such key partners as the World Wildlife Fund (WWF), Missouri Botanical Gardens and Duke University.

In 1990, Madagascar was designated as a priority aid recipient, and assistance increased from $15 million in 1989 to $40 million in 1993. Madagascar was one of the first countries to qualify for the African Growth Opportunity Act (AGOA) "Wearing Apparel" provisions, allowing the growth of a significant textile and garments export sector in Madagascar.  A coup d’état in 2009 resulted in Madagascar’s loss of AGOA privileges.  On June 26, 2014, following the restoration of democratic rule, President Obama announced the reinstatement of Madagascar’s eligibility for benefits under AGOA, with immediate effect.

U.S. assistance in Madagascar has contributed to a population census and family planning programs; conservation of Madagascar's remarkable biodiversity; private sector development; agriculture activities; democracy and governance initiatives; greater access to higher quality basic education; and media training. Madagascar became the very first country with a Millennium Challenge Account compact when it signed an agreement worth $110 million in April 2006, although the compact was terminated due to the 2009 coup d’état and resulting political crisis.