High-intensity anthropogenic activities have greatly altered the estuarine-shelf depositional processes of sediments, and the intensity and frequency of the impacts of human interventions have far exceeded the natural development of estuarine systems. Since the reform and opening up, human activities such as dams, sand mining, channel dredging, and reclamation have already caused anomalous changes in the dynamical–sedimentary–geomorphological processes of the Lingdingyang Estuary (LE). Analyzing the impact of high-intensity anthropogenic activities on sedimentary processes and the hydrodynamic environment through sedimentary records can provide a scientific basis for predicting the evolution of the estuary and the sustainable development of the Guangdong–Hongkong–Macao Greater Bay Area. The aims of this study are to reveal the impact of varying intensity human activities across different periods on depositional pattern and conduct a preliminary investigation into the spatial differences in sedimentary characteristic attributed to human activities. Two cores (LD11 and LD13) located in the LE were selected for continuous scanning of high-resolution XRF, grain size, and 210Pbex dating tests, and scrutinized with the previous studies of the historical process of human activities in the LE. The results show the following: (1) The abrupt alterations in 210Pbex, geochemical indices, and grain size in LD13 happened in close proximity to the 95 cm layer, suggesting a shift in the sedimentary environment during 1994. (2) In the context of the continuous reduction in water and sediment flux into the LE after 1994, the large-scale and high-intensity human activities like sand mining, channel dredging, and reclamation are responsible for the sedimentation rate increase rather than decrease, the coarsening of sediment fractions, the frequent fluctuations in Zr/Rb, Zr/Al, Sr/Fe, and Sr/Al ratios, and the increase in anomalous extremes. (3) Sedimentary records found in locations varying in anthropogenic intensities differ greatly. Compared with the nearshore siltation area, the grain size composition in the channel area is noticeably coarser and exhibits a wider range of grain size variations. The 210Pbex is strongly perturbed and the vertical distribution is disturbed; the phenomenon of multiple inversions from the surface downwards is shown, making it impossible to carry out sedimentation rate and dating analysis, and the geochemical indicators have changed drastically without any obvious pattern. The evidence of the human activities can be retrieved in the sedimentary record of the estuary and provide a different angle to examine the impacts of the human activities.