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Abstract Ginger (Zingiber officinale Roscoe), one of the most economically valuable plants in the Zingiberaceae family, is widely used as a spice and flavoring agent for beverages, bakery, confectionary, and pharmaceutics. Bacterial wilt disease, caused by Ralstonia solanacearum , is one of the most detrimental production constraints in ginger cultivation. Field cultivation experiments indicated that soil moisture affects the incidence of bacterial wilt disease. However, the relationship between soil moisture and bacterial wilt incidence as well as the mechanism that underlie this infection remain unclear. This study confirms that high soil moisture elevates the susceptibility to R. solanacearum infection; transcriptome sequencing was performed to elucidate the underlying mechanisms. Differential expression indicates that a small number of genes is involved in both the response to high soil moisture as well as post successful R. solanacearum infection; furthermore, a large number of genes is involved in the defense of the infection. In response to high soil moisture, higher ABA contents, and higher expression levels of ABF4 may be related to higher tiller density in ginger. More importantly, WAK16 and WAK3-2 may be determinative genes that weaken the resistance to R. solanacearum in ginger under high soil moisture. The down-regulated expression levels of PRX , CPY , and XET genes indicate that in response to successful R. solanacearum infection, the normal cell wall metabolism may be disturbed and the hypersensitive response may be inhibited. In summary, our study deepens our understanding of the molecular mechanisms of the soil moisture dependent wilt susceptibility of ginger. Graphical abstract Image 1 Highlights • High soil moisture elevates ginger susceptibility to R. solanacearum. • Comparative transcriptome analysis was performed under low and high soil moistures • High ABA and ABF4 related to high tiller density of ginger under high soil moisture. • WAK16 and WAK3-2 may weaken the resistance of ginger to R. solanacearum. • Low PRX, CPY, and XET showed cell wall metabolism was disturbed after infection. [ABSTRACT FROM AUTHOR]