The ongoing global administration of vaccines for coronavirus disease 2019 (COVID-19) means that increasing numbers of patients are likely to present with post-vaccination complications. We describe the first reported case of neuralgic amyotrophy (NA) involving the lumbosacral plexus occurring after AstraZeneca COVID-19 vaccination. The patient presented with acute-onset leg paralysis following administration of the vaccine. Based on the clinical, electrodiagnostic, and radiologic findings, the patient was diagnosed with post-vaccination NA. We speculate that the COVID-19 vaccine elicited an immune-mediated inflammatory response to the injected antigen due to inflammatory immunity in a patient with predisposed susceptibility to NA.