The natural aging (NA) response of a commercial Al-Zn-Mg alloy has been tracked to investigate the effects of solute clusters on its mechanical properties. It is observed that the increase of yield strength during NA is not accompanied by a degeneration of uniform elongation due to the simultaneously enhanced strain hardening ability. As a consequence, the Al-Zn-Mg alloy with dense solute clusters shows a comparative yield strength, better strain hardening ability and ductility relative to its artificially aged counterparts containing precipitates. This positive effect of solute clusters on strain hardening has been systematically studied by tracing the microstructure evolution during deformation through the synchrotron X-ray diffraction and atom probe tomography techniques. We found that the dislocation multiplication dominates over the entire deformation until failure in NA alloys; however, no effect of solute clusters on the dislocation density evolution can be identified. On the other hand, solute clusters themselves dramatically evolve, showing a dissolution-to-coarsening transition during deformation, which can be understood on the basis of a kinetic model. The experimental phenomena strongly suggest that the dislocation storage and strain-induced evolution of solute clusters are far from adequate to account for the observed high strain hardening rate, and contribution from other possible mechanisms are estimated in a semi-quantitative manner.