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Abstract Background Cadmium (Cd), lead (Pb), and mercury (Hg) have been shown to exhibit endocrine disrupting properties. Their effects on women’s reproductive health, however, remain elusive. Here, we investigated associations between blood concentrations of Pb, Cd, Hg, and their mixture and infertility and long-term amenorrhea in women aged 20–49 years using the US National Health and Nutrition Examination Survey (NHANES) 2013–2018 cross-sectional survey. Methods A total of 1,990 women were included for the analysis of infertility and 1,919 women for long-term amenorrhea. The methods of log-transformation and use of quartiles were used to analyze blood heavy metal concentrations. Statistical differences in the covariates between the outcome groups were evaluated using a chi-squared test for categorical variables and a t-test for continuous variables. Multiple logistic regression models were used to examine the associations. Results The blood concentrations of Pb and heavy metal mixtures were significantly higher in ever-infertile women than pregnant women, but the concentrations of Cd and Hg were comparable. After full adjustment, multiple logistic regression analyses revealed a significant and dose-dependent positive association between blood Pb concentrations and women’s historical infertility, a negative association between Cd and women’s long-term amenorrhea, and no associations between Hg and heavy metal mixture and women’s infertility or long-term amenorrhea. Conclusions Our study suggests that exposure to heavy metals exhibit differential associations with history of infertility and amenorrhea, and Pb may adversely impact women’s reproduction and heighten the risks of infertility and long-term amenorrhea.