The long-term morphological evolution process and mechanism of estuaries driven by high-intensity human activities are a hot and frontier scientific issue in estuarine and coastal research. Lingdingyang Estuary (LE) has been disturbed in recent decades by high-intensity anthropogenic forcing. High-intensity human activities have played a major role in the dynamic and geomorphological evolution of the LE, predominantly over the long term. In this study, the morphological evolution pattern of LE from 1955 to 1998 was first simulated using the Telemac-2D long-term morphological evolution model, and the input reduction of the upstream river boundaries was discussed. Then, based on the long-term model, the contribution of different human activities on geomorphic evolution was identified. Finally, the mechanism of high-intensity reclamation on morphological evolution was analyzed. The main findings can be summarized as follows: i) the general geomorphic pattern of LE at the mouth bars and channels are represented reasonably well from 1955 to 1998 when the multiple river boundaries input are reduced to combined seasonal river discharge and the phased daily SSC. Ii) High-intensity reclamation significantly weakened the deposition of ILE (Inner-Lingdingyang Estuary) with the annual deposition volume decreased ~1.33 × 107 m3, resulting in the deposition area narrowing 6–8 km to the south. On the contrary, reclamation enhanced the deposition of OLE (Outer-Lingdingyang Estuary) with the annual deposition volume increased ~5.15 × 106 m3, which enlarged the deposition area. Iii) the sharp decline of sediment discharge in upstream decreased significantly the deposition from 1978 to 1998 with the annual net deposition volume decreased ~1.754 × 107 m3, and the total deposition area of LE narrowed significantly and moved 3–5 km upstream. Iv) the total annual net deposition volume of LE from 1978 to 1998 decreased obviously by 2.084 × 107 m3 under the combined impact of the sharp decline of sediment discharge in upstream and high-intensity reclamation, of which the contribution rate of the sharp decline of sediment discharge in upstream was 61%, and that of high-intensity reclamation was 16% for the whole LE. v) the equilibrium location between runoff and tide caused by high-intensity reclamation moved 4.4 km southward from 1978 to 1998, which was the dominant factor for driving the southward migration of the deposition area during this period. In addition, reclamation resulted in the changes of water surface slope and tidal dynamics, which significantly affected the local geomorphic evolution pattern. The results of this study can improve and enrich the methods of the reduction of river boundary in upstream for long-term geomorphic evolution, and provide reference for the long-term geomorphic simulation of other multi-input estuaries. Our findings are expected to improve the scientific comprehensive management of the Pearl River Estuary and guide the construction of the Guangdong-Hong Kong-Macao Greater Bay Area