Monitoring and quantifying suspended sediment concentrations (SSC) in estuaries such as the Pearl River Estuary (PRE) provide crucial information for environmental processes, hydrological infrastructure, and navigation. Traditional SSC mapping based on in situ investigations lacks the spatial coverage necessitated by detailed analysis. In this study, based on in situ spectral data and SSC measurements, we developed models to quantify SSC based on Landsat TM/OLI and Sentinel-2 imagery. The models were then used to map the SSC distribution in the PRE for the period 1986–2020. The results indicated that SSC in the entire PRE displayed an overall decreasing trend over the past 35 years, but an abnormal increase was also observed in shallow waters near Hengmen. Geographically, the concentration along the west coast is higher than on the east coast, and the central part of Lingding Bay underwent a slight increase. The decreased sediment output from the Pearl River Basin is the major cause of the decreasing changes in SSC. However, the natural factors and human activities such as channel dredging and the construction of artificial facilities can also disturb the spatial distribution of SSC. Regions with a significant decrease in SSC should have special concerns about retaining the PRE’s health and sustainability.