Deltaic channels in river deltas usually play important roles in flood discharge, water supply, and navigation development. Under the combined influences of fluvial and ocean dynamics and human activity, the complex long-term morphological evolution of deltaic channels requires further research, in particular the Modaomen Channel in the Pearl River Delta (PRD), China. This study explored the morphological evolution of the Modaomen Channel from 1962 to 2017. During the study period, the characteristics of the Modaomen Channel after 1977 differed substantially from those before 1977. Before 1977, the channel evolution was mainly controlled by natural processes, with a low silting rate. From 1977 to the present, the channel was strongly influenced by human activities, including sand mining and channel regulation, and then, the channel deepened sharply. Therefore, the deep trough of the channel at the upstream was linked completely to that at the downstream, which became much wider and deeper compared to that in the past. Although the deepening of the channel was beneficial for flood discharge and shipping development, serious environmental problems also developed, including strengthened tidal dynamics and saltwater intrusion. Owing to the severely reduced sediment discharge from the Pearl River and the deepening trend in the channel, the future evolution of the channel and its impacts by extreme flood and storm surge require further detailed investigation and research.