To determine if smoking, obesity, and insulin resistance mediated age at final menstrual period (FMP), we examined anti-Müllerian hormone (AMH), inhibin B, and follicle-stimulating hormone (FSH) as biomarkers of changing follicle status and ovarian aging. We performed a longitudinal data analysis from a cohort of premenopausal women followed to their FMP. Our results found that smokers had an earlier age at FMP (P < 0.003) and a more rapid decline in their AMH slope relative to age at FMP (P < 0.002). Smokers had a lower baseline inhibin B level relative to age at the FMP than nonsmokers (P = 0.002). Increasing insulin resistance was associated with a shorter time to FMP (P < 0.003) and associations of obesity and time to FMP were observed (P = 0.004, in model with FSH). Change in ovarian biomarkers did not mediate the time to FMP. We found that smoking was associated with age at FMP and modified associations of AMH and inhibin B with age at FMP. Insulin resistance was associated with shorter time to FMP independent of the biomarkers. Interventions targeting smoking and insulin resistance could curtail the undue advancement of reproductive aging.