The present study aimed to compare the responses of two rice cultivars to titanium dioxide nanoparticles (nTiO2), in plant performance and root-associated soil microbes, and provide a reference for the selection of nanoparticle-responsive varieties. The field experiment was conducted to study the effects of nTiO2 (applied at 200 mg/kg) on typical Chinese rice cultivars, Wuyunjing23 (WYJ23) and Yongyou2640 (YY2640), for the whole life cycle. We evaluated agronomic and physiological parameters including chlorophyll content and antioxidant enzyme activities at the heading stage, and biomass, Ti, and nutrient elements uptake after harvest. Soil bacterial communities were also measured through 16S rRNA gene sequencing. Exposure to nTiO2 led to neither Ti accumulation nor changed biomass in either cultivar, but it increased root Fe uptake and reduced grain Cu content. Specifically, nTiO2 exposure decreased the chlorophyll content but increased the peroxidase activity in WYJ23; such altered physiology might affect root exudates and further modify bacterial communities. Although nTiO2 did not induce visible phytotoxicity in YY2640, it affected the abundance of bacteria genera associated with N turnover and plant-C-metabolizing (e.g., Geobacter and Gaiella), resulting in changed C and N cycling in the rhizosphere. This study revealed divergent responses of WYJ23 and YY2640 to nTiO2, both in plant physiology and rhizosphere system. nTiO2 induced greater physiological response but affected the rhizosphere little in WYJ23. By contrast, nTiO2 changed soil microbes and enzyme activities without affecting the physiology of YY2640, suggesting its superior adaptivity to nTiO2.