Tsetse-transmitted human African trypanosomiasis (HAT) remains endemic in Uganda. The chronic form caused by (gHAT) is found in north-western Uganda, whereas the acute zoonotic form of the disease, caused by (rHAT), occurs in the eastern region. Cattle is the major reservoir of rHAT in Uganda. These two forms of HAT are likely to converge resulting in a public health disaster. This study examines the intricate and intrinsic links between cattle herd dynamics, livestock trade and potential risk of spread of rHAT northwards. A bio-economic cattle herd model was developed to simulate herd dynamics at the farm level. Semi-structured interviews ( = 310), focus group discussions ( = 9) and key informant interviews ( = 9) were used to evaluate livestock markets ( = 9) as part of the cattle supply chain analysis. The cattle market data was used for stochastic risk analysis. Cattle trade in eastern and northern Uganda is dominated by sale of draft and adult male cattle as well as exportation of young male cattle. The study found that the need to import draft cattle at the farm level was to cover deficits because of the herd structure, which is mostly geared towards animal traction. The importation and exportation of draft cattle and disposal of old adult male cattle formed the major basis of livestock movement and could result in the spread of rHAT northwards. The risk of rHAT infected cattle being introduced to northern Uganda from the eastern region via cattle trade was found to be high (i.e. probability of 1). Through deterministic and stochastic modelling of cattle herd and cattle trade dynamics, this study identifies critical links between livestock production and trade as well as potential risk of rHAT spread in eastern and northern Uganda. The findings highlight the need for targeted and routine surveillance and control of zoonotic diseases such as rHAT.