We propose a multidisciplinary approach to face the interpretation of heterogeneous catalysis with alkaline‐earth metal–organic frameworks (MOFs). Their oxygen‐based polyhedra, which do not exhibit regular geometries, do act as very active Lewis acid sites. Four novel alkaline‐earth MOFs that belong to three different structural types—Mg‐AEPF‐11, Mg‐APF‐12, Ca‐AEPF‐13 and Sr‐APF‐13—are reported, together with their net topologies, and a study of the symmetry distortions around the alkaline‐earth metal polyhedra by using a continuous shape mapping (CShM) description. These MOFs are good catalysts in the selective hydrogenation of styrene. Even more, Sr‐AEPF‐13 shows the best conversions ever published with alkaline‐earth MOFs for the hydrogenation of activated alkenes under mild conditions. A combination of crystallographic and topological analysis and theoretical calculations, together with experimental catalytic results, has been applied to understand the catalytic activity of these four novel alkaline‐earth MOFs. This work demonstrates that the presence of symmetry‐distorted alkaline‐earth polyhedra gives rise to highly catalytic‐active MOFs in the hydrogenation of activated alkenes.