Background Previous studies indicate that transcranial direct current stimulation (tDCS) with anode over motor cortex (M1) and cathode over contralateral supraorbital region (SO) may be effective in reducing pain, but these studies are limited in number and have not focused on older adults with osteoarthritis (OA). Objective To evaluate the preliminary efficacy and safety of M1-SO applied tDCS on clinical pain severity and mobility performance in adults with knee OA pain. Methods Forty 50- to 70-year-old community-dwelling participants with knee OA were randomly assigned to receive five daily sessions of 2 mA tDCS for 20 min (n = 20) or sham tDCS (n = 20). We measured clinical pain severity via Numeric Rating Scale, Western Ontario and McMaster Universities Osteoarthritis Index, and Short-Form McGill Pain Questionnaire. In addition, we measured mobility performance using the 6-Minute Walk Test and the Short Physical Performance Battery. Moreover, we obtained a sensation/safety questionnaire and measured cognition changes using the PROMIS-Applied Cognition-Abilities-Short Form 8a. Results Active tDCS over M1-SO significantly reduced Numeric Rating Scale of pain compared to sham tDCS after completion of the five daily sessions, and remained up to three weeks. No other measures were significantly different from sham. Participants tolerated tDCS over M1-SO well without serious adverse effects or cognition changes. Conclusion Although not consistent in all pain measurements, our findings demonstrate promising clinical efficacy for reduction in pain perception for older adults with knee OA. Trial registration ClinicalTrials.gov Identifier NCT02512393.