IntroductionProductivity of maize (Zea mays L.) is predominantly constrained by diseases, weeds, and insect pests. The northern leaf blight (NLB) disease, caused by Exserohilum turcicum, inflicts significant maize yield losses in the tropics and humid tropics, including Ethiopia. A large‐scale field survey was conducted to assess the spatio‐temporal distribution of maize NLB in southern Ethiopia, and to determine the association of maize farming practices and agro‐ecological factors with NLB epidemics during 2016–2019.Materials and MethodsA total of 814 maize farms were assessed in 12 major maize‐producing districts. During the assessment, data related to the disease, crop, farming practices and agro‐ecological factors were collected. The associations of disease severity with independent factors were determined using the ordinal logistic regression model.ResultsThe results showed that all studied districts and zones recorded high (≥85%) NLB prevalence over the 4 years, and the disease continues to be a major threat to maize production. Variable disease severity was recorded across districts/zones during the study periods. The highest (75.45%) mean severity was recorded from Boreda, followed by Konso (75.36%), Bonke (71.61%) and Derashe (71.30%), while Mihirab Abaya (33.25%) and Arba Minch (38.285%) districts recorded the lowest mean severity. In the multiple regression model, zone, altitude, cropping year, land preparation, NPS fertilization, weeding practice, growth stage and cropping system were highly significantly (p < 0.0001) associated with disease severity.ConclusionMaize cultivation at an altitude of ≤1500 m with intermediate to good weeding practices, recommended NPS (51–100 kg ha–1) fertilization, mixed‐ and intercropping systems, sparse plant (≤20 plants m‒2) population, and vegetative to blistering growth stages had significant relationships with low (≤25, 26%–50%) disease severity, and can be considered as management options to reduce NLB pressure and yield losses to sustainably ensure maize production and productivity.