A family of three o-hydroxyacetophenone derivatives, 2-hydroxy-5-methoxy-4-methylacetophenone (1), 5-methoxy-4-methyl-2-(phenylmethoxy)acetophenone (2) and 2-O-(α-methyl carboethoxy)-5-methoxy-4-methyl-acetophenone (3) were synthesized and their crystal structures were solved using laboratory X-ray powder diffraction data along with a detailed analysis of the Hirshfeld surfaces and 2D-fingerprint plots, facilitating a comparison of intermolecular interactions. The DFT optimized molecular geometries in 1 and 3 agree closely with those obtained from the crystallographic studies. In 2, however, the relative orientation of the two planar phenyl rings as established by the X-ray analysis and quantum mechanical calculations differs by 34.9°. The crystal packing in the compounds is stabilized by an interplay of weak hydrogen bonds, such as C–H⋯O, C–H⋯π and π⋯π interactions, forming supramolecular assemblies. The intermolecular C–H⋯O hydrogen bonds in 1–3 generate C¹₁(6) chains and R_mⁿ(X) rings, which are further connected through C–H⋯π hydrogen bonds and π⋯π interactions to produce parallel molecular sheets built by fused R²₂(24) rings in 1, a three-dimensional architecture with C²₂(16)[R²₂(6)][R²₂(14)] synthons in 2, and a two-dimensional columnar framework in 3.