We report the observation of the generation of dislocations in single-crystal phase-change In2Se3 nanowires under electrical pulses and the impact of these dislocations on electrical properties. Particularly, we correlated the atomic-scale structural characteristics with local electrical resistance variations, by performing transmission electron microscopy and scanning Kelvin probe microscopy on the same nanowires. By coupling the experimental results with first-principles density functional theory calculations, we show that the immobile dislocations are generated via vacancy condensations. Importantly, these dislocations lead to several orders of magnitude increase in the electrical resistance, while maintaining the single crystallinity of the lattice. These results significantly advance the fundamental understanding of the structure-property relation in this phase-change material under transient electrical excitations. From a practical perspective, the significant increase in the electrical resistance, driven by the formation of dislocations, can be exploited as a new electronic state in the single-crystalline phase in this phase-change material.