Anthropogenic stressors can affect individual species and alter species interactions. Moreover, species interactions or the presence of multiple stressors can modify the stressor effects, yet most work focuses on single stressors and single species. Plant-microbe interactions are a class of species interactions on which ecosystems and agricultural systems depend, yet may be affected by multiple global change stressors. Here, we use duckweed and microbes from its microbiome to model responses of interacting plants and microbes to multiple stressors: climate change and tire wear particles. Climate change is occurring globally, and microplastic tire wear particles from roads now reach many ecosystems. We paired perpendicular gradients of temperature and carbon dioxide (CO2) treatments with factorial manipulation of leachate from tire wear particles and duckweed microbiomes. We found that tire leachate and warmer temperatures enhanced duckweed and microbial growth, but caused effects of microbes on duckweed to become negative. However, induced negative effects of microbes were less than additive with warming and leachate. Without tire leachate, we observed that higher CO2 and temperature induced positive correlations between duckweed and microbial growth, which can strengthen mutualisms. In contrast, with tire leachate, growth correlations were never positive, and shifted negative at lower CO2, again suggesting leachate disrupts this plant-microbiome mutualism. In summary, our results demonstrate that multiple interacting stressors can affect multiple interacting species, and that leachate from tire wear particles could potentially disrupt plant-microbe mutualisms.