Coastal lagoons and other estuarine habitats are increasingly exposed to the negative effects of growing human populations with associated intensifications in nutrient loading, harmful algal blooms, pollution, and habitat degradation. We examined population dynamics of Gulf pipefish Syngnathus scovelli in estuarine waters of the Indian River Lagoon, on the Atlantic coast of Florida. Substantial declines in abundance of this sentinel species were concurrent with significant losses of seagrass habitat associated with ongoing harmful algal blooms, and other perturbations during the study period spanning from 1998 to 2018. Moderate declines in S. scovelli were observed with early downward trends in seagrasses ahead of the onset of the precipitous seagrass reductions observed. The massive decline of seagrass habitats in the Indian River Lagoon in recent years had negative influences and was directly linked to population declines we observed in the S. scovelli population. Lack of seagrass habitat essential to this and related syngnathid species may reduce optimum seagrass-associated prey, increase predation by lack of appropriate cover, and increase energetic costs which may be realized through reduced growth rates and potential reproductive impairment. Identification and monitoring of population trends of S. scovelli and related sentinel fish species allow for early implementation of management actions that reduce the impact of anthropogenic pressures on the services that estuarine systems provide to the fishes and fisheries they support.