AbstractHydrazone derivatives ofβ‐dicarbonyl compounds illustrate an integrated configurational and conformational changes, which make them be considered as probe in disclosing H‐bonding importance in hydrogen transfer and switching. The ethyl‐3‐oxo‐butanoate derivatized hydrazones were synthesized by Japp–Klingemann reaction and were characterized in view of chromatographic and spectroscopic behavior employing thin layer chromatography, infrared (IR), ultraviolet‐visible (UV‐vis), and1H and13C nuclear magnetic resonance (NMR) techniques. Conformational isomerization between two possible rotamers along with their tautomeric forms was identified and investigated in detail regarding to resonance‐assisted H‐bonding (RAHB) concept by the referred spectroscopic measurements. Furthermore, substituent impacts were assessed using the acquired spectroscopic data and evaluated for structure–property correlation on the base of Hammett relationships. All of the hydrazone derivatives were found to equilibrate in acetone solution, and more of them existed in one rotameric form in solid state. The aryl substituents influence the intermolecular and intramolecular interactions differently, because the derivatives could be isolated as two distinct crystals only in a few members. Moreover, the RAHB concept was found to stabilize the conformational isomers of the hydrazone derivatives to different degrees leading to distinct equilibrium constant. Quantum chemical calculations (DFT/B3LYP) were also used to characterize the nature of the RAHB and examine the rotameric transformation process and substituent impacts on the rotamerization equilibrium.