Thailand was recognized as having the highest number of lumpy skin disease (LSD) outbreaks in Southeast Asia during 2021. Understanding how LSD outbreaks spread over time and space can provide detailed insight into the distribution and pattern of the disease, allowing for more precise identification of areas with high disease burden. This study aims to explore the spread of LSD among cattle in Thailand during 2021 using spatial and spatio-temporal analyses. Data were analyzed using spatial analysis techniques, including spatial autocorrelation and directional distribution. Additionally, the spatio-temporal models, including space–time permutation (STP) and Poisson with various maximum reported cluster size (MRCS) settings, were applied to the data to determine LSD outbreak clusters. Results showed that a total of 642 LSD outbreaks were reported from March to December 2021. Districts with confirmed cases exhibited spatial autocorrelation, indicating the interconnected spread of LSD across different geographic areas. Furthermore, the disease distribution pattern appeared to extend to the southern and southwestern regions from the northeast. Based on the spatio-temporal models, LSD outbreak clusters were identified in several regions. The STP model tended to identify more clusters with smaller radii compared to the Poisson model. The number of clusters detected varied according to both the model and MRCS setting, underscoring the importance of selecting the most relevant clusters for the effective implementation of disease control strategies. This study was the first of its kind to assess the spatial direction and spatio-temporal distribution of LSD outbreak clusters based on national-level data. Evaluating LSD occurrence through spatial and spatio-temporal analyses can provide valuable insight into its spatio-temporal dynamics, facilitating disease surveillance, control measures, and vector control strategies in Thailand.