The wetland ecosystem along a river in a coastal region has great significance in purifying water bodies, regulating climate, and providing habitat for animals and plants. Studying the effects of human disturbances on the landscape patterns of wetlands is of great significance to the protection and management of an ecosystem. This study used Guannan County and Guanyun County, two counties in China that are located on both banks of the Xinyi River as the study area. The spatiotemporal characteristics of the landscape pattern evolution of wetlands and their relationship with human interference from 2009 to 2020 were analyzed by the landscape dynamic rate, landscape conversion matrix, landscape indices, human disturbance index, and the quadratic regression equation. The results showed that: (1) Except for the increase in the area of beach and paddy fields, the area of other landscape types decreased; (2) the changes in wetlands were heterogeneous and showed different trends in different regions; (3) the boundary shape’s complexity and the landscape pattern’s fragmentation showed a decreasing–increasing trend and the connectivity and the diversity of the landscape decreased; and (4) the human disturbance index increased from 2009 to 2014 and then decreased from 2014 to 2020, declining outward from the places where towns and construction land aggregated. Moreover, there was an inverted U-type relationship with the landscape pattern indices. The findings provide direct, specific, and explicit information and theoretical guidance for the protection of wetlands along the river in the coastal region as well as for the restoration of wetland ecosystem function and the improvement of wetland biodiversity in relevant regions.