The district headquarters at Serere are located approximately 35 kilometres (22 mi) south of Soroti, the largest town in the sub-region.

[1] This location is approximately 205 kilometres (127 mi), by road, northeast of Kampala, the capital of Uganda and the largest city in that country.

Serere District was created by an Act of Parliament and became functional effective 1 July 2010.

Serere District is part of the Teso sub-region, home to an estimated 2.5 million people of Iteso and Kumam ethnicities.

[4] The major ethnicities in the district are: Itesot, Kumam and Bukenye, Bantu peoples.