The flow regime of a river is an important driver of many ecosystem components. However, few studies explore how differences in flow rates and water chemistry can influence communities of parasites and their hosts. Here, we investigate the impact of dissolved oxygen, pH, salinity, water temperature, and river flow on the abundance and prevalence of cymothoid isopod parasitism (Lironeca ovalis) of the Bay Anchovy (Anchoa mitchilli) in the Alafia and Hillsborough rivers of Tampa Bay (Florida). We also explore seasonality by comparing monthly samples preserved throughout 2005–2007. Although both the Alafia and Hillsborough rivers had similar average water temperatures and salinity, and similar wet and dry season cycles, the upstream damming of the Hillsborough River had numerous negative effects on water flow rate, dissolved oxygen content, and acidity. This disruption in water quality corresponded with a lower abundance of anchovy hosts, fewer free-swimming cymothoids, and low prevalence of anchovy parasitism. Anchovies were much more abundant in the Alafia River, but flow negatively affected abundance—a negative effect that could be mitigated by positive changes in water temperature, salinity, and pH. Flow rates also negatively affected free-swimming cymothoid abundance; however, water flow was less important in predicting their parasitism of anchovies. In Alafia, fewer anchovies were parasitized when dissolved oxygen was high and water acidity was low, but more were parasitized during the wet season. These findings corroborate predictions that flow can moderate habitat stability and complexity which, in turn, can impact opportunities for parasitism of host communities.