Cultural heritage worldwide is threatened by microbial biodeterioration. However, we know very little about the global biogeography, ecology, and driving forces of these microbiomes. Here, we provide the first global ecological perspective on the microbiomes of cultural heritage by meta-analyzing ∼1000 microbiomes from contrasting environmental conditions. The results show that the bacterial communities of cultural heritage are mainly influenced by global climate (especially by precipitation patterns), while those fungal communities, dominated by saprotrophs, are largely explained by local habitat conditions. Amongst, phototrophic bacteria (e.g., Alpha-proteobacteria, and Cyanobacteria) and some saprotrophic fungi (e.g., Sordariomycetes, and Dothideomycetes) construct the backbone of the cultural heritage microbiome. In this regard, the biodeterioration of cultural heritage could be pre-estimated and predicted by the ecological calculation on the big data of global environmental conditions and microbiome. In summary, the ecological perspective of the microbiomes on global cultural heritage can help to safeguard the long-term sustainable conservation for future generations.