Little known the connections between soybeans mitogen- activated protein kinase (MAPK) gene expression and the rhizomicrobiome upon invasion of the root pathogen Fusarium oxysporum. To address this lack of knowledge, we assessed the rhizomicrobiome and root transcriptome sequencing of wild and cultivated soybean during the invasion of F. oxysporum. Results indicated F. oxysporum infection enriched Bradyrhizobium spp. and Glomus spp. and induced the expression of more MAPKs in the wild soybean than cultivated soybean. MAPK gene expression was positively correlated with Pseudomonadaceae but negatively correlated with Sphingomonadaceae and Glomeraceae in both cultivated and wild soybean. Specifically, correlation profiles revealed that Pseudomonadaceae was especially correlated with the induced expression of GmMAKKK13-2 (Glyma.14G195300) and GmMAPK3-2 (Glyma.12G073000) in wild and cultivated soybean during F. oxysporum invasion. Main fungal group Glomeraceae was positively correlated with GmMAPKKK14-1 (Glyma.18G060900) and negatively correlated with GmRaf6-4 (Glyma.02G215300) in the wild soybean response to pathogen infection; while there were positive correlations between Hypocreaceae and GmMAPK3-2 (Glyma.12G073000) and between Glomeraceae and GmRaf49-3 (Glyma.06G055300) in the wild soybean response, these correlations were strongly negative in the response of cultivated soybean to F. oxysporum. Taken together, MAPKs correlated with different rhizomicrobiomes indicating the host plant modulated by the host self-immune systems in response to F. oxysporum.