This paper is aimed to propose a three-dimensional model which would be used for investigation on the mechanical behavior of single-layered zinc oxide nanosheets. To develop this model, molecular mechanics is coupled with the density functional theory. Simulating the hexagonal lattices of nanosheets as a hexagonal mechanical structure composed of structural beam elements, the buckling behavior of zinc oxide nanosheets is studied. Effects of different parameters on the stability of armchair and zigzag nanosheets are examined. It is shown that the buckling forces of zigzag nanosheets are slightly greater than those of armchair ones. However, with increasing size of nanosheets the effect of atomic structure on the stability of nanosheets diminishes.By studying the effect of end conditions on the buckling behavior of nanosheets, it is shown the stability of nanosheets is affected significantly by boundary conditions. This paper is aimed to propose a three-dimensional model which would be used for investigation on the mechanical behavior of single-layered zinc oxide nanosheets. To develop this model, molecular mechanics is coupled with the density functional theory. Simulating the hexagonal lattices of nanosheets as a hexagonal mechanical structure composed of structural beam elements, the buckling behavior of zinc oxide nanosheets is studied. Effects of different parameters on the stability of armchair and zigzag nanosheets are examined. It is shown that the buckling forces of zigzag nanosheets are slightly greater than those of armchair ones. However, with increasing size of nanosheets the effect of atomic structure on the stability of nanosheets diminishes. By studying the effect of end conditions on the buckling behavior of nanosheets, it is shown the stability of nanosheets is affected significantly by boundary conditions.