Background. Malaria remains one of the leading health problems of the developing world, and acute kidney injury (AKI) is a well-recognized complication of severe malaria in adults; but the clinical importance of AKI in paediatric severe malaria is not well documented. Knowledge of the prevalence and factors associated with AKI among children with severe malaria is among the key strategies, which can help to reduce the burden of AKI among this vulnerable group. Methodology. A hospital-based prospective cross-sectional descriptive and analytic study of children with severe malaria was carried out at Kiryandongo General Hospital. The study involved 350 children with severe malaria attending the study site from August to October 2021. Questionnaires were administered to caretakers to obtain sociodemographic characteristics. Medical data were obtained through physical examination followed by laboratory tests. Blood samples were tested for creatinine and blood smear for malaria. Data were analyzed using binary logistic regression (bivariate and multivariate) to assess for the factors associated with AKI. A
p
value < 0.05 was considered statistically significant. Results. The mean age of children with severe malaria was
7.0
±
3.8
years, and 54.3% of them were male. Of the 350 children enrolled, 167 had AKI, giving an overall AKI prevalence of 47.7% (95% CI: 42.5-53.0). The factors that were significantly associated with AKI among children with severe malaria included caretaker with no formal education (
aOR
=
21.0
, 95% CI: 1.68–261.18,
p
=
0.018
), caretaker with primary education level (
aOR
=
4.5
, 95% CI: 1.41–14.12,
p
=
0.011
), age of
child
<
5
years (
aOR
=
1.8
, 95% CI: 1.07–2.88,
p
=
0.025
), history of receiving NSAIDs (
aOR
=
5.6
, 95% CI: 2.34–13.22,
p
<
0.001
), moderate anemia (
aOR
=
3.1
, 95% CI: 1.39–6.94,
p
=
0.006
), and severe anemia (
aOR
=
3.8
, 95% CI: 1.66–8.55,
p
=
0.002
). Conclusion. The prevalence of AKI was high among children with severe malaria in Kiryandongo General Hospital. Acute kidney injury among children with severe malaria was associated with low level of education of caretakers, age of children less than 5 years, history of receiving NSAIDs, and anemia. The management of severe malaria should include screening for AKI especially in children under five years of age, anemic, and those who have received NSAIDs.