Celosia argentea Linn. has recently been identified as a hyperaccumulator of both manganese (Mn) and cadmium (Cd). However, the mechanisms by which C. argentea tolerates Mn and Cd toxicity remain unclear. In this study, the spatial distribution of Mn and Cd and their interactions were analyzed using X-ray microfluorescence and the Leadmium Green fluorescent probe. Mn was predominantly localized along the leaf margins, particularly at the apex, whereas in the stem and root, it primarily accumulated in epidermal tissues. The distribution patterns of Mn and calcium (Ca) in C. argentea were inversely correlated, whereas Mn and iron exhibited similar trends. Cd was mainly localized in the leaf veins, vascular bundles at the stem periphery, and vascular cylinders in the roots. Exogenous Mn addition significantly enhanced the fluorescence intensity of Cd in the leaves. Following Mn addition, Cd was detected in the mesophyll tissues and both the upper and lower epidermis, in addition to the leaf veins. Interestingly, exogenous Cd addition changed the distribution pattern of Ca in the leaves of C. argentea. These findings provide novel insights into the mechanisms underlying plant tolerance to Mn and Cd toxicities and help improve the phytoextraction efficiency of Mn and Cd co-contaminated soil.