This study proposes a novel approach for establishing adaptive environmental-flow prescriptions for rivers, channels, and floodways with substantial flow augmentation and a limited decision space using the highly altered Atchafalaya River Basin (ARB) in Louisiana as an example. Development of the ARB into the primary floodway of the Mississippi River and Tributaries Project has contributed to hydrologic changes basin-wide that have altered the river-floodplain interface threatening important ecosystems, notably the expansive baldcypress-water tupelo swamp forests. Current restoration efforts only address the spatial distribution of water in local areas of the basin; however, the timing, frequency, magnitude, and duration of ecologically-important high and low flows are determined at the basin-wide scale by the daily implementation of a federal flow mandate that limits available water management options. We used current hydrologic conditions and established flow-ecology relationships from the literature to develop an environmental flow prescription for the ARB that provides basin-wide flow targets to complement ongoing restoration efforts. Hydrologic analysis of current flows and the flow-ecology requirements for these wetland forests revealed an overlap in the range of flow variability under the current water management model, suggesting environmental flows can be complementary with the desired hydraulic and geomorphic characteristics of the floodway. The result is a first step towards an adaptive flow regime that strives to balance important flow-ecology relationships within a decision space limited by a federal flow mandate. We found high potential for success in managing water for nature while accommodating other management needs for the river.