Helium implantation can cause the formation of a helium gas-bubble superlattice in crystalline materials. Experimental studies of the mechanical response of a material hosting such a superlattice are lacking, especially at the microstructural level. By employing a novel, high-throughput, high-precision nanoscale helium implantation technique, in combination with in-situ transmission electron microscopy nanomechanical testing, we find that the helium-bubble superlattice structure in copper is disordered or maintained depending on whether the material's plasticity occurs by multiple ordinary full dislocations or by deformation twinning. In addition, helium implantation can harden the material significantly: the higher the dose, the larger the yield stress. The measured hardening behavior agrees well with the trend predicted by the Friedel-Kroupa-Hirsch model. Our findings shed new light on understanding the mechanical and microstructural properties of materials subjected to intense helium generation by neutron and alpha-particle bombardment in nuclear fusion, fission or spallation systems.