Cadmium (Cd) is a highly toxic heavy metal that severely impairs plant growth and poses ecological and health risks. Chrysanthemum indicum (L.), a dominant species in Cd-contaminated regions, represents a valuable germplasm for phytoremediation. In this study, we cloned and characterized CiWRKY50, a WRKY transcription factor containing a conserved WRKY domain and C2H2-type zinc finger. CiWRKY50 was localized to the nucleus but lacked intrinsic transcriptional activation activity. Overexpression of CiWRKY50 in Arabidopsis thaliana and C. indicum significantly enhanced Cd tolerance, as shown by reduced root Cd accumulation, improved transport efficiency, lower ROS and MDA levels, and increased chlorophyll, proline, and soluble protein contents. Antioxidant enzyme activities and Cd-chelating compounds (GSH, NPT, PCs) were also upregulated. Furthermore, combined Cd and ABA treatments promoted Cd sequestration in roots and activated ABA-responsive genes (CiABF1, CiABF2, CiABF4), alleviating shoot toxicity. These findings indicate that CiWRKY50 enhances Cd tolerance in association with enhanced ABA-mediated signaling and redox homeostasis, providing new insights for breeding Cd-resistant plants and improving phytoremediation strategies.