The U-28, a modified single engine turbo prop plane used by special operations units, crashed Saturday near Camp Lemonnier, a base used by the US military in the tiny Horn of Africa state.
The Pentagon identified the victims as Captain Ryan Hall, 30, Captain Nicholas Whitlock, First Lieutenant Justin Wilkins, and senior airman Julian Scholten, 26.
The four were based in Hulbert Field, Florida where they were assigned to special operations and intelligence squadrons.
The US Africa Command said the U-28 was on a "routine flight" when it went down six miles (10 kilometers) from the Djibouti International Airport.
The cause of the crash was under investigation.