Twenty-four major and trace elements and the mineralogical composition of four sediment cores along the Pearl River and estuary were analyzed using ICP-AES, ICP-MS, and X-ray diffraction (XRD) to evaluate contamination levels. The dominant minerals were quartz, kaolinite, and illite, followed by montmorillonite and feldspars, while small amounts of halite and calcite were also observed in a few samples. Cluster analysis (CA) and principal component analysis (PCA) were performed to identify the element sources. The highest metal concentrations were found at Huangpu, primarily due to wastewater treatment plant discharge and/or the surreptitious dumping of sludge, and these data differed from those of other sources. Excluding the data from Huangpu, the PCA showed that most elements could be considered as lithogenic; few elements are the combination of lithogenic and anthropogenic sources. An antagonistic relationship between the anthropogenic source metals (K, Ba, Zn, Pb, Cd, Ag, Tl, and U) and marine source metals (Na, Mg, Ti, V, and Ca) was observed. The resulting normalized Al enrichment factor (EF) indicated very high or significant pollution of Cd, Ag, Cu, Zn, Mo, and Pb at Huangpu, which may cause serious environmental effects. Conflicting results between the PCA and EF can be attributed to the background values used, indicating that background values must be selected carefully.