Total suspended solids (TSS) and chlorophyll-a (Chl-a) are critical water quality parameters. Focusing on the Pearl River Estuary and its coastal waters, this study compared the performance of XGBoost- and BPNN-based algorithms in estimating TSS and Chl-a levels. The XGBoost-based algorithm demonstrated better performance and was then used to estimate TSS and Chl-a in the Pearl River Estuary and coastal waters from 2000 to 2021. According to our results, TSS and Chl-a were relatively high mainly in the northwest and low in the southeast. Furthermore, values were high in spring and summer and low in fall and winter, with high values emerging near the estuary of the Pearl River. In summer, a band zone with high Chl-a was observed from south of Yamen to south of Hong Kong. In terms of trends, TSS and Chl-a concentrations in the area around the Hong Kong–Zhuhai–Macao Bridge tended to decrease from 2000 to 2021. As the construction of the bridge began, changes in water flow caused by the bridge piers and artificial islands were influenced, the change in the rate of TSS in the west area of the bridge was greater than 0, and the TSS in the upstream area of the west side changed from decreasing to increasing trends. Concerning Chl-a concentrations, the change in the rate in the downstream area of the west side of the bridge was greater than 0. The study may provide a helpful example for similar estuarine and coastal waters in other coastal areas.