Objective The putative effect of lesion-induced brain damage on post-stroke upper limb motor impairment can be estimated by overlaying a patient's lesion or its surrogate with key motor areas. We assessed the predictive value of imaging-based brain damage measures for cross-sectional upper limb motor impairment and subsequent upper limb motor outcome after stroke. Methods In 47 stroke patients, upper limb motor impairment was evaluated with the Upper-Extremity Fugl-Meyer Assessment (UE-FMA) at 2 weeks (2W) and 3 months (3M) post-stroke. Given each patient's lesion identified at 2W, we considered the disconnectome, estimated as an ensemble of structural and functional connections passing through the lesion, as a surrogate of the lesion. The lesion load and the disconnectome load were measured by overlaying the lesion and disconnectome with the corticospinal tract (CST) and motor cortex (MC), and their association with the UE-FMA score at 2W and 3M was assessed. Results Whereas the disconnectome loads on the CST and MC were better in predicting the UE-FMA score at 2W, the lesion load on the CST was better in predicting the UE-FMA score at 3M. Furthermore, when the CST lesion load was combined with the UE-FMA score at 2W, the UE-FMA score at 3M was better predicted, with smaller generalization error, than by using either measure alone. Conclusions The combination of the CST lesion load and baseline upper limb motor impairment would provide a tailored fusion of imaging and clinical measures for more accurate motor outcome prediction.