Trace quantities of pharmaceuticals (including carbamazepine and sertraline) are continuously discharged into the environment, which causes concern among scientists and regulators regarding their potential long-term impacts on aquatic ecosystems. These compounds and their metabolites are continuously interacting with the orgranisms in various life stages, and may differentially influence development of embryo, larvae, juvenile, and adult stages. To fully understand the potential ecological risks of two candidate pharmaceutical chemicals (carbamazepine (CBZ) and sertraline (SERT)) exposure on survival, growth and reproduction of Ceriodaphnia dubia in three sucessive generations under static renewal toxicity test, a multigenerational approach was taken. Results indicate that SERT exposure showed higher sensitivity to chronic exposure to C. dubia growth and reproduction than CBZ exposure. The lowest concentration to affect fecundity and growth was at 50 µg L-1 SERT in the first two generations. These parameters become more sensitive during the third generation where the LOEC was 4.8 µg L-1. The effective concentrations (EC50) for the number of offspring per female, offspring body size, and dry weight were 17.2, 21.2, and 26.2 µg SERT L-1, respectively. Endpoints measured in this study demonstrate that chronic exposure of C. dubia to SERT leads to effects that occur at concentrations an order of magnitude higher than predicted environmental concentrations indicating potential transgenerationals effects. Additionally, a process-based dynamic energy budget (DEB) model is implemented to predict the simulated effects of chronic toxicity of SERT and CBZ to C. dubia individual behavior at laboratory condition. The model‘s output indicates the ecotoxicological mode of action of SERT exposure, which acts on feeding or assimilation with an effect that rapidly saturates at higher concentrations. Offspring size decreases with the toxic effects on feeding, and offspring number is thus less affected than total investment in reproduction. Consequently, CBZ affects direclty in reproduction which are captured by DEBtox model as increased embryonic hazard and reproduction cost as well as growth and maintenance costs. Furthermore, stress factor linearly increased not only with increasing chemical concentrations but also with exposure time. The DEBtox model establishes a cumulative life history consequence of multigenerational exposure to CBZ and SERT. This approach provides a tool to which to understand the effect of chemical to the individual organism and predict the population level effects in ecological risk assessment of the emerging contaminants.