The plant microbiome plays crucial roles in nutrient acquisition, growth and health of plants, and has the potential to reduce dependence of the crops on fertilizers and pesticides. Plant domestication shows a significant impact on composition and functions of the microbiome. However, the mechanisms underlying this process are not well understood. Here, the paper is presented to summarize impacts of the variation of the plant in cultivar and genotype, root exometabolite and habitat, while the plants are being domesticated on composition and functions of the microbiome. Multifaceted comparison shows:(1) that domestication affects microbial diversity significantly and most of the plant microbial communities decrease in diversity during domestication; wild crops might attract more microbial communities that are beneficial to the resistance of pathogenic bacteria:and variation of the plant in cultivar and genotype affects composition of the rhizosphere microbiome and symbiotic relationship of the microbiome with the plant; (2) that changes in root exometabolite affect nutrient acquisition of the microbes and domestication weakens chemical defense of the plant; (3) Relative to the microbiome in the soil of croplands, the one in the virgin soil habitat is composed of more diverse and unique microbes. To sum up, the change in the plant rhizosphere microbiome is the result of the comprehensive interactions of multiple factors during the plant domestication process. Revealing the impacts of plant domestication on functions of the microbiome and restoring the beneficial plant-microbe connections and properties that may have got lost during plant domestication, can facilitate the development of new microbiome-based breeding strategies.