Math anxiety (MA) seems to result from an interaction of genetic vulnerability with negative experiences learning mathematics. Although mathematics achievement does not substantially differ between the sexes, MA levels are usually higher in girls. Molecular genetic markers of MA vulnerability have been seldom explored. This article examines the contribution of the monoamine oxidase A gene (MAOA) to MA and to sex differences in MA. Five hundred and sixty‐eight third to fifth graders were genotyped for the MAOA‐LPR polymorphism (a repetitive element in MAOA promoter that has been associated with MAOA enzymatic activity), and assessed on general cognitive ability, mathematics achievement, and the cognitive and affective dimensions of MA. MAOA‐LPR genotypes were classified as high (MAOA‐H) or low (MAOA‐L) according to their predicted enzymatic activity. Mixed models controlling for effects of school, sex, general cognitive ability, and mathematics achievement were evaluated. The best fitting model included school, math achievement, sex, MAOA‐LPR, and the MAOA‐LPR by sex interaction. This indicated that under the MAOA‐H dominant model, anxiety toward mathematics interacted with the MAOA genotype: girls with an MAOA‐L genotype exhibited higher levels of MA, with a small but significant effect. The association between MAOA‐L genotype and MA in girls may represent an example of developmental plasticity. Third to fifth graders self‐reported on the cognitive and affective dimensions of math anxiety (MA) and were genotyped for the MAOA‐LPR polymorphism, a repetitive element in the MAOA promoter associated with MAOA enzymatic activity. Interactions between genotype, sex, and MA were analyzed under different genetic models. Girls with the low activity (MAOA‐L), as opposed to boys and girls with the high activity (MAOA‐H) genotype, reported higher levels of affective MA.