The National Livestock Resources Research Institute (NaLIRRI) owes its origins to the colonial era when the East African Trypanosomiasis Research Organisation (EATRO) was founded in 1956 with a mandate to conduct research on Tsetse flies and Trypanosomiasis in both human and animals across Uganda, Kenya and Tanzania under the jurisdiction of the East African Common Services Organisation which later became the East African Community.

EATRO was eventually handed over to Uganda Government in 1977 after the collapse of the East African Community and was renamed Uganda Trypanosomiasis Research Organisation (UTRO). UTRO was mandated to conduct research on tsetse flies, human and animal Trypanosomiasis in Uganda. In 1992, UTRO was merged with the then Animal Health Research Centre at Entebbe to form Livestock Health Research Institute (LIRI) to handle livestock health and theriogenology, including, sleeping sickness in man.

The National Agricultural Research Act 2005 of Uganda established a National Agricultural Research System (NARS) for Uganda comprising of semi-autonomous National Agricultural Research institutes to manage and conduct strategic agricultural research. The Act mandates NaLIRRI as the public agricultural research institute responsible for research and related services in Livestock Health, Nutrition, Breeding, Socio-economics, Marketing and Apiculture.