Fine particulate matter in the lower atmosphere (PM_2.5) continues to be a major public health problem globally. Identifying the key contributors to PM_2.5 pollution is important in monitoring and managing atmospheric quality, for example, in controlling haze. Previous research has been aimed at quantifying the relationship between PM_2.5 values and their underlying factors, but the spatial and temporal dynamics of these factors are not well understood. Based on random forest and Shapley additive explanation (SHAP) algorithms, this study analyses the spatiotemporal variations in selected key factors influencing PM_2.5 in Zhejiang Province, China, for the period 2000–2019. The results indicate that, while factors influencing PM_2.5 varied significantly during the period studied, SHAP values suggest that there is consistency in their relative importance as follows: meteorological factors (e.g., atmospheric pressure) > socioeconomic factors (e.g., gross domestic product, GDP) > topography and land cover factors (e.g., elevation). The contribution of GDP and transportation factors initially increased but has declined in the recent past, indicating that economic and infrastructural development does not necessarily result in increased PM_2.5 concentrations. Vegetation productivity, as indicated by changes in NDVI, is demonstrated to have become more important in improving air quality, and the area of the province over which it constrains PM_2.5 concentrations has increased between 2000 and 2019. Mapping of SHAP values suggests that, although the relative importance of industrial emissions has declined during the period studied, the actual area positively impacted by such emissions has actually increased. Despite developments in government policy, greater efforts to conserve energy and reduce emissions are still needed. The study further demonstrates that the combination of random forest and SHAP methods provides a valuable means to identify regional differences in key factors affecting atmospheric PM_2.5 values and offers a reliable reference for pollution control strategies.