Colonization by Lactobacillus in the female genital tract is thought to be critical for maintaining genital health. However, little is known about how genital microbiota influence host immune function and modulate disease susceptibility. We studied a cohort of asymptomatic young South African women and found that the majority of participants had genital communities with low Lactobacillus abundance and high ecological diversity. High-diversity communities strongly correlated with genital pro-inflammatory cytokine concentrations in both cross-sectional and longitudinal analyses. Transcriptional profiling suggested that genital antigen-presenting cells sense gram-negative bacterial products in situ via Toll-like receptor 4 signaling, contributing to genital inflammation through activation of the NF-κB signaling pathway and recruitment of lymphocytes by chemokine production. Our study proposes a mechanism by which cervicovaginal microbiota impact genital inflammation and thereby might affect a woman’s reproductive health, including her risk of acquiring HIV. •Most African women studied had genital communities with low Lactobacillus abundance•Unlike the gut, high-diversity cervicovaginal communities are pro-inflammatory•Specific bacteria induce cytokine production from genital APCs and epithelial cells Vaginal colonization by a single bacterium, Lactobacillus, is considered healthy. Kwon and colleagues show that in a cohort of asymptomatic African women, the majority have high-diversity genital bacterial communities that are closely associated with local inflammation. This work suggests specific genital bacteria might increase HIV acquisition risk in women.