Analyzing the current status of forest loss and its causes is crucial for understanding and preparing for future forest changes and the spatial pattern of forest loss. We investigated spatial patterns of forest loss in South Korea and assessed the effects of various factors on forest loss based on spatial heterogeneity. We used the local Moran’s I to classify forest loss spatial patterns as high–high clusters, low–low clusters, high–low outliers, and high–low outliers. Additionally, to assess the effect of factors on forest loss, two statistical models (i.e., ordinary least squares regression (OLS) and geographically weighted regression (GWR) models) and one machine-learning model (i.e., random forest (RF) model) were used. The accuracy of each model was determined using the R², RMSE, MAE, and AICc. Across South Korea, the forest loss rate was highest in the Seoul–Incheon–Gyeonggi region. Moreover, high–high spatial clusters were found in the Seoul–Incheon–Gyeonggi and Daejeon–Chungnam regions. Among the models, the GWR model was the most accurate. Notably, according to the GWR model, the main factors driving forest loss were road density, cropland area, number of households, and number of tertiary industry establishments. However, the factors driving forest loss had varying degrees of influence depending on the location. Therefore, our findings suggest that spatial heterogeneity should be considered when developing policies to reduce forest loss.