Multiple anthropogenic stressors act simultaneously on the environment, with consequences different from those caused by single-stressor exposure. We investigated how the combination of the invasive mussel Limnoperna fortunei and a widely applied herbicide, Roundup Max®, affected freshwater microscopic communities and water quality. Further, we compared these results with those induced by the combination of the mussel and technical-grade glyphosate. We carried out a 34-day experiment in outdoor mesocosms, applying the following six treatments: 6 mg L(-1) of technical-grade glyphosate (G), the equivalent concentration of glyphosate in Roundup Max® (R), 100 mussels (M), the combination of mussels and herbicide either in the technical-grade or formulated form (MG and MR, respectively), and control (C). Herbicides significantly increased total phosphorus in water; R and MR showed greater initial total nitrogen and ammonium. R increased picoplankton abundance and caused an eightfold increase in phytoplankton, with high turbidity values; G had a lower effect on these variables. Herbicide-mussel combination induced an accelerated dissipation of glyphosate in water (MG 6.36 ± 0.83 mg G g DW(-1) day(-1) and MR 5.16 ± 1.26 mg G g DW(-1) day(-1)). A synergistic effect on ammonium was observed in MR but not in MG. MR and MG had an antagonistic effect on phytoplankton, which showed a drastic reduction due to grazing, as revealed by M. We provide evidence of differential effects of Roundup Max® and technical-grade glyphosate over water quality and microscopic communities, and in combination with mussels. However, in the combination of mussels and herbicides, mussels seem to play a leading role. In the presence of L. fortunei, the effects of higher nutrient availability provided by herbicides addition were counteracted by the filtration activity of mussels, which released nutrients, grazed on picoplankton and phytoplankton, and boosted the development of other primary producers, periphyton and metaphyton.