Incorporating a variety of microalgae into wastewater treatment is considered an economically viable and environmentally sound strategy. The present work assessed the growth characteristics of Chlorella sorokiniana during cultivation in balanced synthetic media and domestic wastewater. Increasing the NH4+–N concentration to 360 mg L−1 and adding extra PO43−–P and SO42−–S (up to 80 and 36 mg L−1, respectively) contributed to an increase in the total biomass levels (5.7–5.9 g L−1) during the cultivation of C. sorokiniana in synthetic media. Under these conditions, the maximum concentrations of chlorophylls and carotenoids were 180 ± 7.5 and 26 ± 1.4 mg L−1, respectively. Furthermore, when studying three types of domestic wastewaters, it was noted that only one wastewater contributed to the productive growth of C. sorokiniana, but all wastewaters stimulated an increased accumulation of protein. Finally, the alga, when growing in optimal unsterilized wastewater, showed a maximum specific growth rate of 0.73 day−1, a biomass productivity of 0.21 g L−1 day−1, and 100% NH4+–N removal. These results demonstrate that the tested alga actively adapts to changes in the composition of the growth medium and accumulates high levels of protein in systems with poor-quality water.