This study investigated the mobility and availability of Cd, Pb, and As pollution in the sediments of the Xijiang River Basin, China. The speciation analysis and ecological risk assessment of Cd, Pb, As in 21 sediment samples from the Xijiang River basin were studied by the sequential extraction technique, the enrichment factor (EF), the geo-accumulation index (I_geo), the potential ecological risk index (RI), the potential ecological risk factor (E_rⁱ), the risk assessment code (RAC), and the modified potential ecological risk index (MRI) assessment method. Metal speciation analysis indicated that the exchangeable and carbonate fraction were the primary binding phase for Cd in the sediment. However, the residual fraction was the major host for Pb and As. The Cd, Pb, and As speciation were highly correlated with Mn, organic matter (OM), carbonate (Carb), and pH. The RAC and MRI results showed that the mobility and availability of Cd, Pb, and As in the sediment followed the order of Cd > As > Pb. The higher mobility of Cd posed an elevated environmental risk. Moreover, it was found that the Diaojiang River had high ecological risk levels. Principal component analysis (PCA) and redundancy analysis (RDA) revealed that the mining industry mainly contributed to the enrichment of Cd, Pb, and As. This study provides a better understanding to predict and possibly find ways to control pollution of Cd, Pb, and As in sediments of such basins.