The use of LED-illuminated photobioreactors with microalgae has been extensively studied for wastewater treatment. Most studies have used isolated microalgae species; however, this practice does not match the reality of conditions in wastewater treatment plants. Operational conditions that promote greater growth of algal biomass and that remove pollutants most effectively are disputed in the literature. In this context, LED–illuminated photobioreactors with microalgae were evaluated using multivariate analysis in order to optimize removal of pollutants (nitrogen, phosphorus, and carbonaceous organic matter). Three variables were evaluated: operating time, LED wavelength, and luminous flux intensity. A microalgae consortium was used in the photobioreactor. In addition to the LED-illuminated photobioreactors, control photobioreactors illuminated by sunlight were also operated. Using the results obtained in the optimization, a scaled-up reactor approximately 8.5 times larger in volume was operated to evaluate if the behavior would be maintained. The best operational conditions for the removal of pollutants were observed in LED-illuminated photobioreactors operated under a light intensity of 700 μmol·m−2s−1 for 15 days. Under these conditions, it was possible to remove 89.97% of carbonaceous organic matter, 86.50% of nitrogen, and 30.64% of phosphorus. The scaled-up photobioreactor operated with similar performance.