The district headquarters at Moyo, are located approximately 158 kilometres (98 mi), by road, northeast of Arua, the largest city in the sub-region.

[1] This location lies approximately 476 kilometres (296 mi), by road, northwest of Kampala, Uganda's capital and largest city.

In recent years the district has stagnated in isolation as the Second Sudanese Civil War raged to the north and the insurgency of the Lord's Resistance Army made the direct road south to the national capital of Kampala perilous.

The 2005 Sudanese peace agreement and reduced activities of the LRA have raised hopes that Moyo District will again become the prosperous transit area for cross-border trade that it once was.

In the first decade of the 2000s, Moyo District experienced rapid population growth, primarily from refugees fleeing war in South Sudan.