Complex oxides have a number of roles in nuclear energy applications and thus understanding their response to irradiation is critical for predicting performance and developing new materials. In particular, significant work has been devoted to the amorphization response of pyrochlores, a complex oxide related to fluorite that has been identified as a potential nuclear waste form. Previous work has shown a correlation between the amorphization resistance and the ease of cation disorder in chemically different pyrochlores. Here, using transmission electron microscopy and x-ray diffraction, we show that the opposite behavior is observed in another complex oxide, spinels, in which amorphization resistance is inversely correlated to the ability of the cation sublattice to disorder. Using density functional theory and accelerated molecular dynamics, we attribute the different response in these two materials to structural cation vacancies that exist in spinel that facilitate kinetic pathways to relaxation that are not possible in pyrochlore.