A hybrid QM:QM method that combines MP2 as high-level method on cluster models with density functional theory (PBE+D2) as low-level method on periodic models is applied to adsorption of methane and ethane on the MgO(001) surface for which reliable experimental desorption enthalpies are available. Two coverages are considered, monolayer (every second Mg2+ ion occupied) and one quarter coverage (one of eight Mg2+ ions occupied). Structure optimizations are performed at the hybrid MP2:(PBE+D2) level, with the MP2 energies and forces counterpoise corrected for basis set superposition error and extrapolated to the complete basis set limit. For the MP2 calculations on the adsorbate monolayer a two-body expansion of the lateral molecule–molecule interactions is applied. Higher order correlation effects are evaluated at the hybrid MP2:(PBE+D2) equilibrium structures as coupled cluster [CCSD(T)] − MP2 differences adopting smaller basis sets. The final adsorption energies obtained for monolayer coverage are −14.0 ± 1.0 and −23.3 ± 0.6 kJ mol−1 for CH4·MgO(001) and C2H6·MgO(001), respectively. They agree within 1 kJ mol−1 – well within chemical accuracy limits – with reference energies of −15.0 ± 0.6 and −24.4 ± 0.6 kJ mol−1, respectively. The latter have been derived from measured desorption enthalpy barriers, taking zero-point vibrational energy (ZPVE) and thermal enthalpy contributions into account.