In the heavy petroleum industry, the development of efficient demulsifiers for the effective breaking of interfacially active asphaltenes (IAA)-stabilized water-in-heavy oil (W/HO) emulsions is a highly attractive but challenging goal. Herein, a novel nitrogen and oxygen containing demulsifier (JXGZ) with strong hydrogen bonding has been successfully synthesized through combining esterification, polymerization and amidation. Bottle tests indicated that JXGZ is effectual in quickly demulsifying the IAA-stabilized W/HO emulsions; complete dehydration (100%) to the emulsions could be achieved in 4 min at 55 °C using 400 ppm of JXGZ. In addition, the effects of demulsifier concentration, temperature and time on the demulsification performance of JXGZ are systematically analyzed. Demulsification mechanisms reveal that the excellent demulsification performance of JXGZ is attributed to the strong hydrogen bonding between JXGZ and water molecules (dual swords synergistic effect under hydrogen bond reconstruction). The interaction of the “dual swords synergistic effect” generated by two types of hydrogen bonds can quickly break the non-covalent interaction force (π-π stacking, Van der Waals force, hydrogen bonds) of IAA at the heavy oil–water interface, quickly promote the aggregation and coalescence of water molecules and finally achieve the demulsification of W/HO emulsions. These findings indicate that the JXGZ demulsifier shows engineering application prospects in the demulsification of heavy oil–water emulsions, and this work provides the key information for developing more efficient chemical demulsifiers suitable for large-scale industrial applications.