Its largest communities are the cities of Galena, in the west, and Fort Yukon, in the northeast.

Its population density, at 0.0449 inhabitants per square mile (0.0173/km2), is the lowest in the United States.

12.95% reported speaking an Athabaskan language at home; of these 35.26% spoke Gwich'in and 10.94% Koyukon.

School districts include:[20] Like other areas of the sparse Alaskan Bush with large Alaska Native majorities, the Yukon-Koyukuk Census Area often favors the Democratic Party relative to the state as a whole.

Though it voted Republican in all presidential elections in the 2000s, it has supported the Democrats more recently by nearly 30-point margins.