Domestication of crops has changed how crops shape their associated microbial communities compared to their progenitors. However, studies testing how crop domestication-driven differences in rhizosphere microbial communities affect plant health are limited mostly to specific symbiont pairings. By conducting a soil manipulation greenhouse study, we examined plant growth and yield in response to differences in microbial communities and nutrient availability across a variety of wild, landrace, and cultivated potatoes. Coupled with this, we conducted 16S and ITS amplicon sequencing to examine plant host and soil treatment-driven differences in microbial community composition on potato plant roots. Our results found the plant response to microbes (PRM) is context-dependent. In low nutrient conditions, landraces responded positively to the presence of live soil microbial inocula. Conversely, modern potato varieties positively responded in high nutrient conditions. Amplicon sequencing found differences in bacterial communities due to environmental and temporal factors. However, potato clade (e.g. Andigenum, Chiletanum, S. berthaulti, and Modern) alone did not lead to differences in microbial communities that accounted for PRM differences. Differences in PRM between landraces and modern potatoes, and the correlation of PRM to microbial diversity, suggest that domestication has altered the S. tuberosum response to rhizosphere microbiomes.