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Prior studies suggest that prenatal per- and polyfluoroalkyl substances (PFAS) exposures are associated with shorter breastfeeding duration. Studies assessing PFAS mixtures and populations in North America are sparse. We quantified PFAS concentrations in maternal plasma collected during pregnancy in the New Hampshire Birth Cohort Study (2010–2017). Participants completed standardized breastfeeding surveys at regular intervals until weaning (n = 813). We estimated associations between mixtures of 5 PFAS and risk of stopping exclusive breastfeeding before 6 months or any breastfeeding before 12 months using probit Bayesian kernel machine regression. For individual PFAS, we calculated the relative risk and hazard ratio (HR) of stopping breastfeeding using modified Poisson regression and accelerated failure time models respectively. PFAS mixtures were associated with stopping exclusive breastfeeding before 6 months, primarily driven by perfluorooctanoate (PFOA). We observed statistically significant trends in the association of perfluorohexane sulfonate (PFHxS), PFOA, and perfluorononanoate (PFNA) (p-trends≤0.02) with stopping exclusive breastfeeding. Participants in the highest PFOA quartile had a 28% higher risk of stopping exclusive breastfeeding before 6 months compared to those in the lowest quartile (95% Confidence Interval: 1.04, 1.56). Similar trends were observed for PFHxS and PFNA with exclusive breastfeeding (p-trends≤0.05). PFAS were not associated with stopping any breastfeeding before 12 months. In this cohort, we observed that participants with greater overall plasma PFAS concentrations had greater risk of stopping exclusive breastfeeding before 6 months and associations were driven largely by PFOA. These findings further support the growing literature indicating that PFAS may be associated with shorter duration of breastfeeding. [ABSTRACT FROM AUTHOR]