Purpose Northern Leaf Blight (NLB), caused by Exserohilum turcicum, is a major constraint to maize production in Ethiopia. This study aimed to investigate the epidemiological drivers and spatial patterns of NLB across major maize-growing regions to inform integrated management strategies.Methods A field survey was conducted across 18 districts in Oromia, Amhara, and SNNPR regions over two cropping seasons (2021–2022), encompassing 1,080 farms. Disease severity was quantified using Percent Severity Index (PSI) and Lesion Area (LA). Spatial, agronomic, and environmental data were analyzed using chi-square tests, correlation analysis, and logistic regression.Results Pronounced spatial and temporal variations in NLB severity were observed. Oromia exhibited the highest overall disease pressure (PSI: 63.0%), followed by SNNPR (62.1%) and Amhara (60.6%). At the zonal level, Sidama recorded the most severe infections (PSI: 70.6%). Moist and semi-moist mid-altitude zones showed the highest disease pressure (PSI: 70.3%), attributed to cooler temperatures and higher rainfall (> 1,200 mm). Temporal trends showed higher severity in 2021 (PSI: 64.0%) than 2022 (60.2%). Cropping systems and cultivar selection significantly modulated disease outcomes. Sole cropping exacerbated severity (PSI: 68.4%), while intercropping reduced risk (PSI: 54.2%). Susceptible cultivars like BH540 (PSI: 77.1%) suffered severe infections, whereas resistant hybrids such as BH661 (PSI: 51.7%) mitigated impact. Logistic regression identified late planting (OR = 42.53), susceptible cultivars (OR = 24.51), and high-risk agro-ecology (OR = 7.22–16.07) as the top risk factors.Conclusion This study highlights the multifactorial nature of NLB epidemics. Effective management requires spatially-targeted integrated strategies combining resistant cultivars, optimized planting schedules, diversified cropping systems, and balanced nutrition to enhance maize productivity and safeguard smallholder livelihoods in Ethiopia.