This study investigated the phycoremediation abilities of Chlorella vulgaris (microalga) and Anabaena variabilis (cyanobacterium) for the detoxification of polluted river water. Lab-scale phycoremediation experiments were conducted for 20 days at 30 °C using the microalgal and cyanobacterial strains and water samples collected from the Dhaleswari river in Bangladesh. The physicochemical properties such as electrical conductivity (EC), total dissolved solids (TDS), biological oxygen demand (BOD), hardness ions, and heavy metals of the collected water samples indicated that the river water is highly polluted. The results of the phycoremediation experiments demonstrated that both microalgal and cyanobacterial species significantly reduced the pollutant load and heavy metal concentrations of the river water. The pH of the river water was significantly raised from 6.97 to 8.07 and 8.28 by C. vulgaris and A. variabilis, respectively. A. variabilis demonstrated higher efficacy than C. vulgaris in reducing the EC, TDS, and BOD of the polluted river water and was more effective at reducing the pollutant load of SO42− and Zn. In regard to hardness ions and heavy metal detoxification, C. vulgaris performed better at removing Ca2+, Mg2+, Cr, and Mn. These findings indicate that both microalgae and cyanobacteria have great potential to remove various pollutants, especially heavy metals, from the polluted river water as part of a low-cost, easily controllable, environmentally friendly remediation strategy. Nevertheless, the composition of polluted water should be assessed prior to the designing of microalgae- or cyanobacteria-based remediation technology, since the pollutant removal efficiency is found to be species dependent.