Density functional theory (B3LYP-D3, M06-2X) has been used to calculate the structures, interaction energies and vibrational frequencies of a set of 93 methanol–water clusters of different type (cubic, ring, spiro, lasso, bicyclic), size and composition. These interaction energies have been used within the framework of the Quantum Cluster Equilibrium Theory (QCE) to calculate cluster populations as well as thermodynamic properties of binary methanol–water mixtures spanning the whole range from pure water to pure methanol. The necessary parameters a_mf and b_xv of the QCE model were obtained by fitting to experimental isobars of MeOH–H₂O mixtures with different MeOH content. The cubic and spiro motifs dominate the distribution of methanol–water clusters in the mixtures with a maximum of mixed clusters at x(MeOH) = 0.365. Reasonable agreement with experimental data as well as earlier molecular dynamics simulations was found for excess enthalpies H^E, entropies S^E as well as Gibbs free energies of mixing G^E. In contrast, heat capacities C_p and C^E _p showed only poor agreement with experimental data.