Repetitive transcranial magnetic stimulation (rTMS) targeting the left dorsolateral prefrontal cortex (DLPFC) is a treatment option for patients with medication-resistant major depressive disorder (MDD). However, antidepressant response is variable and there are currently no response predictors with sufficient accuracy for clinical use. Here we report on results of an observational open-label study to determine whether the modulatory effect of 10 Hz motor cortex (MC) rTMS is predictive of the antidepressant effect of 10 Hz DLPFC rTMS. Fifty-one medication-resistant MDD patients were enrolled for a 10-day treatment course of DLPFC rTMS and antidepressant response was assessed according to post-treatment reduction of the 17-item Hamilton Rating Scale for Depression score. Prior to treatment, we assessed the modulation of motor evoked potential (MEP) amplitude by MC rTMS. We measured MEP's to single pulse TMS using surface electromyography, before and after MC rTMS, and calculated MEP modulation as the change of mean MEP amplitude after MC rTMS. MEP modulation proved to be a robust predictor of reduction of clinician-rated depression severity following the course of DLPFC rTMS: larger MC rTMS-induced increase of corticospinal excitability anticipated a better antidepressant response. These findings suggest that MC rTMS-induced modulation of corticospinal excitability warrants further evaluation as a potential predictive biomarker of antidepressant response to left DLPFC 10 Hz rTMS, and could inform future developments of rTMS to treat depression.