Municipal effluents are recognized as major sources of pollutants that could compromise fish health and reproduction. The purpose of this study was to examine and compare the reproductive toxicity of low- and high-risk municipal effluents to fathead minnows (Pimephales promelas) exposed for 12 weeks in the laboratory. After the exposure period, reproductive success was determined by following changes in the total number of eggs, egg hatchability/survival and time to hatch. In parallel, the expression of the following was also assessed in adults to gain insights into the pathways involved in toxicity: estrogen receptor alpha (ERα), androgen receptor (Ar1), pregnane X receptor (PXR1), vitellogenin (VTG), CYP3A4 and 17β-hydroxysteroid dehydrogenase (HSD). The results revealed that in the high- and low-risk effluents, egg laying followed a biphasic response, with an initial increase in egg laying followed by a decrease at higher concentrations and stronger amplitudes with the high-risk effluent. Hatching success (i.e., release of viable fish fry) was directly proportional to the decrease in egg production with no hatching of viable fish at 10% and 20% for both effluents. VTG gene expression was significantly increased in females, reaching levels 4 and 3 orders of magnitude greater than in the controls for the high- and low-risk effluent, respectively. VTG gene expression was also found in males but at lower expression levels than for the females. The expression of ERα was significantly correlated with VTG levels, which suggests the presence of estrogenic compounds in municipal effluents. This was further supported by the increased expression of CYP3A4, which is involved in the biotransformation of steroid-like and pharmaceutical compounds. In conclusion, municipal effluents have the capacity to reduce reproduction in fathead minnows and involve estrogenic effects. The high-risk effluent generally displayed stronger effects than the low-risk effluent.