Brassicaceae seed meal (SM) soil amendment has been utilized as an effective strategy to control the biological complex of organisms, which includes oomycetes, fungi, and parasitic nematodes, that incites the phenomenon termed apple replant disease. Soil-borne disease control attained in response to Brassicaceae SM amendment is reliant on multiple chemical and biological attributes, including specific SM-generated modifications to the soil/rhizosphere microbiome. In this study, we conducted a comparative analyses of apple root gene expression as influenced by rootstock genotype combined with a seed meal (SM) soil amendment. Apple replant disease (ARD) susceptible (M.26) and tolerant (G.210) rootstocks cultivated in SM-amended soil exhibited differential gene expression relative to corresponding non-treated control (NTC) orchard soil. The temporal dynamics of gene expression indicated that the SM-amended soil system altered the trajectory of the root transcriptome in a genotype-specific manner. In both genotypes, the expression of genes related to plant defense and hormone signaling were altered in SM-amended soil, suggesting SM-responsive phytohormone regulation. Altered gene expression was temporally associated with changes in rhizosphere microbiome density and composition in the SM-treated soil. Gene expression analysis across the two rootstocks cultivated in the pathogen-infested NTC soil showed genotype-specific responses indicative of different defensive strategies. These results are consistent with previously described resistance mechanisms of ARD “tolerant” rootstock cultivars and also add to our understanding of the multiple mechanisms by which SM soil amendment and the resulting rhizosphere microbiome affect apple rootstock physiology. Future studies which assess transcriptomic and metagenomic data in parallel will be important for illuminating important connections between specific rhizosphere microbiota, gene-regulation, and plant health.