Advancements in transmission electron microscopy allow us to draw correlations between evolving matrix chemistry environments and the resulting dislocation structures that form. Such phenomena are essential in predicting the lifetime of neutron reactor components, but are not well understood at the fundamental level. We investigate the effect of nano-scale matrix chemical evolution in Zircaloy-2 on dislocation formation after emulating commercial reactor irradiation conditions on a proton beamline. Similarity in the dislocation type, morphology, density and evolution between the different irradiation types establishes proton irradiation in this regard. For the first time, we observe chemical segregation of Fe, Ni and Cr to a-loop positions in basal traces and the segregation of Sn in alternate rows, anticorrelated to the positions of the light transition elements. The resulting layered structure with a periodicity of ∼50 nm creates an even greater anisotropy than that usually associated with HCP materials. Concurrent analysis of chemical effects and dislocation spatial relationships provides evidence that may explain the delayed onset of c-loop nucleation and accelerated dimensional instability regimes in its dependence on the alignment of a-loops parallel to the trace of the basal plane. This demonstrates the applicability of chemical-structural correlations towards key research questions regarding deformation behaviour. Display omitted