Background: Although there are studies that have examined brain functional reorganization following upper-limb amputation, understanding of the brain changes that occur in people with lower-limb amputation is limited. Objective: To investigate modifications in the brain following lower-limb amputation. Methods: We included case-control studies that evaluate neuroplasticity in the central nervous system using neuroimaging techniques. A literature search was conducted using MEDLINE, CINAHL, Web of Science, Scopus, and Cochrane. Results: Eleven articles were included (total n = 204 people with unilateral lower-limb amputation). These studies showed an increase in cerebellar gray matter volume in prosthesis users, as well as a decrease in thickness of the premotor cortex, orbitofrontal cortex, temporo-occipital junction, precentral gyrus, visual areas, and somatosensory cortex. Regarding white matter, the trials observed a decrease in the integrity at the corona radiata, the connections between the premotor areas, the fronto-occipital fasciculus and the corpus callosum. In addition, a decreased functional connectivity between cortical and subcortical areas has been described. Conclusions: Lower-limb amputation causes changes in several brain structures that may occur in the absence of pain and regardless of prosthesis use. The modifications observed include thinning or loss of gray matter volume, decrease in the integrity of the white matter connections between brain structures and changes in the functional connectivity between cortical and subcortical areas.