© 2019, Springer Nature B.V. The contamination of the Sonora River with 40,000 m3 of toxic leachate released from a copper mine on August 6, 2014, was considered the worst environmental disaster of the mining industry in Mexico, exceeding safety levels in the concentrations of heavy metals and arsenic. To explore the potential association of the toxic release with subfecundity, by comparing time to pregnancy (TTP) of women with different levels of exposure at municipalities located along the Sonora River watershed, just 35 km south of the Arizona–Mexico border. Data from 235 pregnancies were included in a retrospective cohort study. Exposure was measured whether pregnancy occurred before or after the disaster and included a non-exposed community outside the watershed. Pregnancies were also compared between communities according to the concentration-level gradient of water pollutants found in the river. Fecundability odds ratios (fORs) were calculated using discrete time analogue of Cox’s proportional hazard models. Multiple analysis included all pregnancies with TTP of no more than 12 months, only first-time pregnancy, or excluding women with TTP = 1. The probability for pregnancy decreased after the disaster (fOR 0.55, 95% CI 0.31, 0.97), when the residency was located mid-or-downstream the watershed (fOR 0.37, 95% CI 0.15, 0.91), when reported chicken consumption, when mining was the father’s occupation, and when surface water was reported to be used for crop irrigation and for animal consumption. There was a decrease in fecundity on women exposed to the contaminated river. There is a need for more studies to prove these findings and to broaden the knowledge of other possible adverse health effects associated with this environmental disaster.