Self-renewal and pluripotency of the embryonic stem cells (ESCs) state is established and maintained through inter-connected “regulatory networks” that build up with several ESC-specific transcription factors (TFs) and epigenetic regulators to control chromatin organization and gene regulation. Although much has been learned, the roles of epigenetic factors in these networks are incompletely defined. In this study, we focused on histone demethylases (HDMs, is a class of epigenetic regulators, which consist of ~20 individual members that remove methyl group(s) from the particular lysine residue(s) of histone tails to modulate chromatin architecture for gene regulation) to dissect their “combinatorial functions” in gene regulatory networks for the maintenance of ESC state that is currently unknown. Moreover, no such studies have performed to address the combinatorial functions of all HDMs in any biological systems to date. To address this, we have generated genome-wide occupancy/binding data of 20 known HDMs, so-called, “histone demethylome” (HDMome) map. This reveals that “multiple HDMs” share the same binding sites at the genome-wide level both at promoters and enhancers. Particularly, KDM1A-KDM4B-KDM6A co-occupy at the enhancer regions, and KDM4A-KDM4C-KDM5B-JARID2 co-occupy at the promoter regions. Comprehensive computational and biochemical analyses demonstrate that KDM1A-KDM4B-KDM6A collaborate with ESC-TFs and belongs to the ESC CORE module/network (active); whereas KDM4A-KDM4C-KDM5B-JARID2 work with polycomb repressive complexes 1, 2 (PRC1 and PRC2) and belongs to the PRC module/network (repressive). Furthermore, detailed molecular studies show that predominantly KDM1A-KDM6A collectively regulate H3K27ac and H3K4me1/me2 at the enhancers; while KDM4A-KDM4C-KDM5B-JARID2 cooperatively regulate H2AK119ub1(of PRC1), as well as H3K4me2/me3 and H3K27me3 bivalent marks (of PRC2) at the promoters for gene regulation. Hence, our findings uncover the combinatorial functions of HDMs, which orchestrates the transcription control for the maintenance of steady-state of mESCs.