We tested whether long-term neurodegeneration of substantia nigra (SN) secondary to disconnection by supra-tentorial infarcts can be quantified with iron-sensitive imaging and contributes to clinical outcome. 181 stroke patients (75 striatum infarcts, 106 other locations) were prospectively evaluated at 24-to-72h and at one-year clinically and with MRI to quantify iron through R2*. We showed a delayed increase of R2* within SN that was strongly and independently associated with infarct location along known anatomic projections from SN. Such increase of R2* was an independent contributor of poor motor outcome. Iron-sensitive imaging can monitor neurodegeneration non-invasively within SN and potentially other areas.