As part of the ecological risk assessment associated with radionuclides in freshwater ecosystems, toxicity of waterborne uranium was recently investigated in the microcrustacean Daphnia magna over a three-generation exposure (F0, F1, and F2). Toxic effects on daphnid life history and physiology, increasing over generations, were demonstrated at the organism level under controlled laboratory conditions. These effects were modeled using an approach based on the dynamic energy budget (DEB). For each of the three successive generations, DEBtox (dynamic energy budget applied to toxicity data) models were fitted to experimental data. Lethal and sublethal DEBtox outcomes and their uncertainty were projected to the population level using population matrix techniques. To do so, we compared two modeling approaches in which experimental results from F0, F1, and F2 generations were either considered separately (F0-, F1-, and F2-based simulations) or together in the actual succession of F0, F1, and F2 generations (multi-F-based simulation). The first approach showed that considering results from F0 only (equivalent to a standard toxicity test) would lead to a severe underestimation of uranium toxicity at the population level. Results from the second approach showed that combining effects in successive generations cannot generally be simplified to the worst case among F0-, F1-, and F2-based population dynamics.