Increasing demand for energy and reduction of carbon dioxide emissions has revived interest in nuclear energy. Designing materials for radiation environments necessitates a fundamental understanding of how radiation-induced defects alter mechanical properties. Ion beams create radiation damage efficiently without material activation, but their limited penetration depth requires small-scale testing. However, strength measurements of nanoscale irradiated specimens have not been previously performed. Here we show that yield strengths approaching macroscopic values are measured from irradiated ~400 nm-diameter copper specimens. Quantitative in situ nanocompression testing in a transmission electron microscope reveals that the strength of larger samples is controlled by dislocation–irradiation defect interactions, yielding size-independent strengths. Below ~400 nm, size-dependent strength results from dislocation source limitation. This transition length-scale should be universal, but depends on material and irradiation conditions. We conclude that for irradiated copper, and presumably related materials, nanoscale in situ testing can determine bulk-like yield strengths and simultaneously identify deformation mechanisms.