Numerous studies have shown that a healthy reproductive tract microbiota is crucial for successful reproduction and that its composition is influenced by various environmental and host factors. However, it is not known whether the reproductive microbiota is also shaped by the major histocompatibility complex (MHC), a family of genes essential to differentiate ‘self’ from ‘non-self’ peptides to initiate an adaptive immune response. We tested the association between the follicular fluid microbiome and MHC genes in 27 women. Women with higher MHC diversity had a higher microbiome diversity, characterized by bacteria commonly associated with vaginal dysbiosis. Women with similar MHC genes were also similar in their microbiome composition, indicating that MHC composition may be a key factor in determining the bacterial assemblage in the reproductive tract. Finally, the composition of the follicular fluid microbiome was similar to the vaginal microbiome, suggesting that numerous bacteria of the vagina are true inhabitants of the follicular fluid or that vaginal microbiota contaminated the follicular fluid microbiota during transvaginal collection. Collectively, our results demonstrate the importance of host genetic factors in shaping women's reproductive microbiota and they open the door for further research on the role of microbiota in mediating MHC-related variation in reproductive success.