Arbuscular mycorrhizal fungi (AMF) affect cadmium (Cd) accumulation and tolerance in host plants. However, the effects of AMF on Cd accumulation and phytotoxicity and their underlying mechanism in apples remain uncharacterized. In this study, the comprehensive physiological and molecular responses of uninoculated and Rhizophagus intraradices-inoculated Malus hupehensis Rehd. rootstocks exposed to 0 or 300 μM Cd were investigated. AMF inoculation mitigated Cd-induced growth and photosynthesis inhibition and nutrient ion disorders. It also lowered the concentrations of Cd in all tissues and reduced Cd transport to the shoots. Compared to uninoculated apple plants, those inoculated with mycorrhizal fungi reduced the mobility and toxicity of Cd by altering its form and binding it to the cell walls of the roots and leaves. AMF inoculation ameliorated Cd stress by altering endogenous phytohormone levels and triggering enzymatic and non-enzymatic antioxidant systems. Transcriptome analysis revealed that the differentially expressed genes (DEGs) associated with AMF under Cd stress regulated carbohydrate and amino acid biosynthesis and metabolism, as well as phytohormone biosynthesis and signal transduction. Furthermore, AMF inoculation downregulated certain genes involved in Cd uptake and transport while upregulating other genes involved in detoxification. These results suggest that AMF alleviate Cd phytotoxicity by orchestrated physiological and transcriptomic regulation in M. hupehensis Rehd., providing valuable insights into the efficacy of AMF inoculation in improving the heavy metal resistance of fruit trees.