“Two Americans survived the crash and were rescued by Colombian military forces and taken to a hospital in Bogota,” the US Southern Command said.
“There is no indication the plane was shot down,” it added.
The Miami, Florida-based command said the DH-8 turboprop aircraft crashed Saturday near the city of Capurgana near the border with Colombia.
It said the identities of the three Americans were being withheld pending notification of their families.
The Panamanian was identified as Air National Guard Lieutenant Lloyd Nunez.
The aircraft was contracted by the US government to monitor and detect drug trafficking routes along the coast of Central America, the command said.
The Panamanian National Naval Air Service said the aircraft was conducting an “anti-drug operation” in the border area between Colombia and Panama when it went down.
The flights are part of “Operation Martillo,” a joint program with Colombia and Panama, according to the command.
“We express our sympathies to the families of the deceased and are particularly saddened by the loss of a Panamanian Air National Guardsman,” said General John Kelly, the head of the command, which is responsible for US military activities in Latin America.
“We also want to thank the Colombians for their outstanding rescue and recovery efforts,” he said in a statement.