Discovering new materials with tailored chemical properties is vital for advancing key technologies in catalysis and energy conversion. One strategy is the modification of a material's crystal structure, and new methods allow for the synthesis and stabilization of potential materials in a range of crystal polymorph structures. We assess the potential reactivity of four metastable oxide polymorphs of MO₂ (M = Ru, Rh, Pt, Ir) transition metal oxides. In spite of the similar local geometry and coordination between atoms in the metastable polymorphic and stable rutile structure, we find that polymorph reactivities cannot be explained by strain alone and offer tunable reactivity and increased stability. Atom-projected density of states reveals that the unique reactivity of polymorphs are caused by a redistribution of energy levels of the t_2g-states. This structure–activity relationship is induced by slight distortions to the M–O bonds in polymorphic structures and is unattainable by strain. We predict columbite IrO₂ to be more active than rutile IrO₂ for oxygen evolution.