Despite the prevalence of central post-stroke pain (CPSP), pain-causing brain lesions remain incompletely understood. In 17 CPSP patients receiving invasive neuromodulation, we utilized voxelwise odds-ratio mapping and normative resting state fMRI to identify high-risk pain hotspots and describe functional networks associated with CPSP lesions and analgesic stimulation. Highest-risk CPSP hotspots were located in somatosensory thalamus/white matter and connected to a network comprising anterior cingulate cortex, insula, thalamus, and inferior parietal lobule. Posterior insula and thalamus were also coupled to therapeutic deep brain stimulation volumes. These findings elucidate CPSP’s topography and connectivity while informing the network-level mechanism of analgesic neuromodulation.