On December 15, 1989, Noriega sought and was given by the legislature the title of chief executive officer of the government. The Noriega-led assembly declared that a state of war with the United States existed. The next day Panamanian soldiers killed an unarmed U.S. Marine officer dressed in civilian clothes.

Retaliation by the United States was quick and decisive. On December 17, U.S. President George Bush ordered troops to Panama, with the subsequently announced aims of seizing Noriega to face drug charges in the United States, protecting American lives and property, and restoring Panamanian liberties. The initial attack took place in darkness on the morning of December 20 and was focused primarily on Noriega's headquarters in Panama City. U.S. forces quickly overcame most organized resistance, but in the following days numerous Panamanian soldiers and civilians looted shops in Panama City and Colón, and some 2,000 U.S. reinforcements were flown in to help establish order. The number of Panamanians killed in the operation was estimated at 200-300 combatants (soldiers and paramilitaries) and some 300 civilians; 23 U.S. soldiers also were killed. Hundreds from both nations were wounded.

On the first day of the invasion, Endara and his two vice presidents were sworn in to head the government of Panama. Noriega took refuge in the Vatican nunciature (embassy) in Panama, until he surrendered to U.S. authorities on January 3, 1990, and was then transported to Miami, Florida. There he stood trial, was convicted on a host of charges, and was sentenced to a U.S. prison. In Panama and also France, Noriega was charged with various crimes, including murder, but no enduring efforts were made to have him extradited.