Prior studies suggest neurodevelopmental impacts of polybrominated diphenyl ethers (PBDEs), but few have examined diagnosed developmental disorders.Our aim was to determine whether prenatal exposure to brominated flame retardants (BFRs) is associated with autism spectrum disorder (ASD) or intellectual disability without autism (ID).We conducted a population-based case-control study including children with ASD (n=545) and ID (n=181) identified from the California Department of Developmental Services and general population (GP) controls (n=418) from state birth certificates. ASD cases were matched to controls by sex, birth month, and birth year. Concentrations of 10 BFRs were measured in maternal second trimester serum samples stored from routine screening. Logistic regression was used to calculate crude and adjusted odds ratios (AOR) for associations with ASD, and separately for ID, compared with GP controls, by quartiles of analyte concentrations in primary analyses.Geometric mean concentrations of five of the six congeners with ≥55% of samples above the limit of detection were lower in mothers of children with ASD or ID than in controls. In adjusted analyses, inverse associations with several congeners were found for ASD relative to GP (e.g., quartile 4 vs. 1, BDE-153: AOR=0.56, 95% CI: 0.38, 0.84). When stratified by child sex (including 99 females with ASD, 77 with ID, and 73 with GP), estimates were consistent with overall analyses in boys, but in the opposite direction among girls, particularly for BDE-28 and -47 (AOR=2.58, 95% CI: 0.86, 7.79 and AOR=2.64, 95% CI: 0.97, 7.19, respectively). Similar patterns overall and by sex were observed for ID.Contrary to expectation, higher PBDE concentrations were associated with decreased odds of ASD and ID, though not in girls. These findings require confirmation but suggest potential sexual dimorphism in associations with prenatal exposure to BFRs. https://doi.org/10.1289/EHP1079.