A cross-sectional study was conducted to estimate the seroprevalence of lumpy skin disease (LSD) in the different agro-climatic zones prevailing in Ethiopia. A total of 2368 serum samples were collected from 42 kebeles located in 15 districts and tested using indirect fluorescent antibody test (IFAT) and virus neutralization test (VNT). The herd and animal true LSD serological prevalence were estimated in each agro-climate zone using a Bayesian model. The intra-cluster correlation coefficient (ICC) was evaluated using a random-effect model. According to the serological prevalence estimations, LSD affected differently the three agro-climatic zones considered. Herd level seroprevalence was higher in the midland agro-climate zone 64% (95% CI: 53-74) as compared to the highland 26% (95% CI: 17-36) and the lowland 50% (95% CI: 40-60) agro-climates. Animal level seroprevalence in infected herds was also higher in the midland agro-climate zone 31% (95% CI: 24-40) than in the highland and lowland zones (24% (95% CI: 18-31) and 23% (95% CI: 18-29), respectively). Higher ICC value in the highland agro-climate zone implies that increased sample sizes should be particularly required for this zone in future studies to estimate LSD prevalence or incidence with a desired precision level. This seroprevalence study also suggests that the prevalence of LSD infection in Ethiopia is higher than what has been previously reported. In the light of these updated estimations, we discuss options to trigger appropriate control measures in the future.