Sex differences are established through the combined effects of sex chromosomes and sex hormones, however, the contribution of sex chromosome-linked genes to skeletal sex differences remains poorly understood. Utx, an X chromosome–encoded gene, functions as a histone demethylase that removes the repressive H3K27me3 histone mark, thereby upregulating gene expression. In this study, we investigated the role of Utx in chondrocyte differentiation to elucidate the mechanisms underlying skeletal sex differences. To this end, we generated limb mesenchymal cell-specific Utx conditional knockout (cKO) mice using the Prrx1-Cre driver and compared them with littermate control (Ctrl) mice. In female cKO mice, we observed a significant reduction in long bone length at both 1 and 8 weeks of age compared to female Ctrl mice, whereas no such difference was detected in males. Phenotypic analysis of primary cultured chondrocytes revealed enhanced extracellular matrix production and mineralization in cKO cells, regardless of sex. To identify direct Utx target genes involved in chondrocyte differentiation, we performed RNA-Seq and CUT&Tag analysis for H3K27me3. Integrative analysis of these datasets identified 24 genes whose expression was downregulated during chondrocyte differentiation in association with persistent H3K27me3 marks in Utx-deficient cells. Gene ontology analysis revealed that these genes were significantly enriched in the category of “Ossification.” Given that these phenotypic effects were predominantly observed in females, our findings suggest that Utx plays a pivotal role in regulating chondrocyte differentiation and skeletal development in females by controlling mineralization through epigenetic mechanisms. In contrast, the milder phenotype observed in males may be attributable to compensatory activity by Uty, a Y chromosome–encoded homolog of Utx. Taken together, these results indicate that Utx contributes to the establishment of skeletal sex differences via histone modification-mediated epigenetic regulation of gene expression, even during early developmental stages before the influence of sex hormones.