The aggregation propensity of melamine molecules in aqueous solutions in a range of melamine concentrations is investigated by means of a combination of theoretical and experimental approaches. It is observed that the hydrogen bonding interactions of sp nitrogen atoms of one melamine with sp nitrogen atoms of another melamine play a major role in the melamine association. This finding is complemented by the observed favorable electrostatic energies between melamine molecules. The estimation of the orientational probability of melamine aromatic ring rules out any role of π-π interaction in melamine association. Further, the quantum chemical calculations suggest that a melamine molecule prefers to bind with another like molecule with a dihedral angle ranging from 36° to 46°. We have also determined the dimer existence autocorrelation functions to investigate the melamine-dimer stability with time in aqueous solution. Our results are well validated by the experimental findings (Chapman, R. P.; Averell, P. R.; Harris, R. R. Solubility of Melamine in Water. Ind. Eng. Chem. 1943, 35, 137-138. Ahromi, A. J.; Moosheimer, U. Oxygen Barrier Coatings Based on Supramolecular Assembly of Melamine. Macromolecules 2000, 33, 7582-7587. Yang, C.; Liu. Y. Studying on the Steady-State and Time-Resolved Fluorescence Characteristics of Melamine. Spectrochim. Acta A 2010, 75, 1329-1332. Mircescu, N. E.; Oltean, M.; Chis, V.; Leopold, N. FTIR, FT-Raman, SERS and DFT study on Melamine. Vib. Spectrosc. 2012, 62, 165-171. Makowski. S. J.; Lacher. M.; Schnick. W. Supramolecular Hydrogenbonded Structures between Melamine and N-Heterocycles. J. Mol. Struct. 2012, 1013, 19-25. Li, Z.; Chen, G.; Xu, Y.; Wang, X.; Wang, Z. Study of the Structural and Spectral Characteristics of CN(NH)(n = 1-4) Clusters. J. Phys. Chem. A 2013, 117, 12511-12518. Li, P.; Arman, D. H.; Wang, H.; Weng, L.; Alfooty, K.; Angawi, R. F.; Chen. B. Solvent Dependent Structures of Melamine: Porous or Non-porous. Cryst. Growth Des. 2015, 15, 1871-1875. Chen, J.; Lei, X.; Peng, B. Study on the Fluorescence Spectra of Melamine in Pure Milk. J. Opt. 2017, 46, 183-186.). Moreover, the thermodynamics of melamine association reveals that the association process is essentially driven by enthalpy, and this enthalpy-driven phenomenon is also confirmed by the experimental isothermal titration calorimetry measurements.