The Daliao river system (DRS) and its estuary have been long affected by intensive industrial, urban and agricultural activities. The objectives of this study were to evaluate the Sb contamination and determine the regional geochemical baseline (RGB) of Sb for the sediment of the DRS watershed. Surface sediment samples were collected at 35 sites and analyzed for total Sb, Sc, Mn, Al, Fe, and Ca. Results indicate that the average Sb content was 0.68 mg kg−1 (0.27–1.12 mg kg−1), lower than that of world sediments. Sb was enriched in the estuarine sediment relative to the upper continental crust (UCC), but it was not enriched relative to the local soil background contents. Thus, Sb in the estuarine sediment mainly originates from natural sources. The content of Sb was highly correlated to the contents of Fe and Sc in the estuarine sediment, with correlation coefficients of 0.915 and 0.925, respectively. Therefore, Fe and Sc can be used as the conservative reference elements to develop the RGB of Sb in the estuarine sediment. The detailed RGB equation of Sb for the estuarine sediment is Sb (mg kg−1) = 0.234 × Fe% + 0.064 and Sb (mg kg−1) = 0.066 × Sc (mg kg−1) + 0.100. This RGB equation may be used to evaluate Sb contamination in the estuarine and riverine sediment of the DRS watershed.