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Background Cytochrome P450s play crucial roles in various biosynthetic reactions. Ginger (Zingiber officinale), which is often threatened by Ralstonia solanacearum, is the most economically important crop in the family Zingiberaceae. Whether the cytochrome P450 complement (CYPome) significantly responds to this pathogen has remained unclear. Methods Transcriptomic responses to R. solanacearum and soil moisture were analyzed in ginger, and expression profiles of the CYPome were determined based on transcriptome data. Results A total of 821 P450 unigenes with ORFs ≥ 300 bp were identified. Forty percent soil moisture suppressed several key P450 unigenes involved in the biosynthesis of flavonoids, gingerols, and jasmonates, including unigenes encoding flavonoid 3′-hydroxylase, flavonoid 3′,5′-hydroxylase, steroid 22-alpha-hydroxylase, cytochrome P450 family 724 subfamily B polypeptide 1, and allene oxide synthase. Conversely, the expression of P450 unigenes involved in gibberellin biosynthesis and abscisic acid catabolism, encoding ent-kaurene oxidase and abscisic acid 8′-hydroxylase, respectively, were promoted by 40% soil moisture. Under R. solanacearum infection, the expression of P450 unigenes involved in the biosynthesis of the above secondary metabolites were changed, but divergent expression patterns were observed under different soil moisture treatments. High moisture repressed expression of genes involved in flavonoid, brassinosteroid, gingerol, and jasmonate biosynthesis, but promoted expression of genes involved in GA anabolism and ABA catabolism. These results suggest possible mechanisms for how high moisture causes elevated susceptibility to R. solanacearum infection.