Background: Fatigue is a common and debilitating feature of multiple sclerosis (MS) that remains without reliably effective treatment. Transcranial direct current stimulation (tDCS) is a promising option for fatigue reduction. We developed a telerehabilitation protocol that delivers tDCS to participants at home using specially designed equipment and real-time supervision (remotely supervised transcranial direct current stimulation (RS-tDCS)). Objective: To evaluate whether tDCS can reduce fatigue in individuals with MS. Methods: Dorsolateral prefrontal cortex left anodal tDCS was administered using a RS-tDCS protocol, paired with 20 minutes of cognitive training. Here, two studies are considered. Study 1 delivered 10 open-label tDCS treatments (1.5 mA; n = 15) compared to a cognitive training only condition (n = 20). Study 2 was a randomized trial of active (2.0 mA, n = 15) or sham (n = 12) delivered for 20 sessions. Fatigue was assessed using the Patient-Reported Outcomes Measurement Information System (PROMIS)—Fatigue Short Form. Results and conclusion: In Study 1, there was modest fatigue reduction in the active group (−2.5 ± 7.4 vs −0.2 ± 5.3, p = 0.30, Cohen’s d = −0.35). However, in Study 2 there was statistically significant reduction for the active group (−5.6 ± 8.9 vs 0.9 ± 1.9, p = 0.02, Cohen’s d = −0.71). tDCS is a potential treatment for MS-related fatigue.