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Freshwater protected areas (FPAs) are increasingly important for biodiversity conservation, given the intensive use of these systems for water, energy and food production. However, the fisheries benefits of FPAs are not well understood, particularly for indiscriminate fisheries typical of tropical systems. Here we report the results of a model that tests the fisheries effects of no-take protected areas in conditions unique to indiscriminate riverine/floodplain systems. The model has a generalized form applicable to a wide range of systems. We report the results of the general model, as well as those from a specialized form parameterized for the Tonle Sap lake, Cambodia. Both the general and Tonle Sap versions of the model show that FPAs can pay important fisheries benefits, especially where it is difficult to control fishing mortality through gear restrictions or other means. The harvest and profit benefit response curves have similar shapes, with additional FPAs paying high dividends at less than approximately 50% FPA coverage, and then truncating and declining thereafter. In the specific setting of the Tonle Sap of Cambodia, FPAs would pay a large increase in harvest because current FPA coverage is low. It may be counterintuitive to community fisheries managers in Cambodia that the best way to increase harvest is to restrict fishing, but at very high levels of fishing effort, reducing effort or area fished will improve both harvest and profit. In Cambodia, it may make sense to maximize harvest rather than profit because fishers living in poverty need to maximize protein offtake, but the benefits of FPAs remain. Similar considerations may apply in many freshwater and indiscriminate fisheries.