General anesthesia (GA) can produce analgesia (loss of pain) independent of inducing loss of consciousness, but the underlying mechanisms remain unclear. We hypothesized that GA suppresses pain in part by activating supraspinal analgesic circuits. We discovered a distinct population of GABAergic neurons activated by GA in the mouse central amygdala (CeA GA neurons). In vivo calcium imaging revealed that different GA drugs activate a shared ensemble of CeA GA neurons. CeA GA neurons also possess basal activity that mostly reflect animals’ internal state rather than external stimuli. Optogenetic activation of CeA GA potently suppressed both pain-elicited reflexive and self-recuperating behaviors across sensory modalities, and abolished neuropathic pain-induced mechanical (hyper-)sensitivity. Conversely, inhibition of CeA GA activity exacerbated pain, produced strong aversion, and cancelled the analgesic effect of low-dose ketamine. CeA GA neurons have widespread inhibitory projections to numerous affective pain-processing centers. Our study points to CeA GA as a potential powerful therapeutic target for alleviating chronic pain.