The gut microbiome has been linked to host obesity; however, sex-specific associations between microbiome and fat distribution are not well understood. Here we show sex-specific microbiome signatures contributing to obesity despite both sexes having similar gut microbiome characteristics, including overall abundance and diversity. Our comparisons of the taxa associated with the android fat ratio in men and women found that there is no widespread species-level overlap. We did observe overlap between the sexes at the genus and family levels in the gut microbiome, such as Holdemanella and Gemmiger; however, they had opposite correlations with fat distribution in men and women. Our findings support a role for fat distribution in sex-specific relationships with the composition of the microbiome. Our results suggest that studies of the gut microbiome and abdominal obesity-related disease outcomes should account for sex-specific differences.