In this study, we demonstrate a novel approach for fabricating copper nanodomes (CuNDs) by combining of soft lithography, nanosphere lithography, physical vapor deposition (PVD) and electrochemical deposition methods. The 3D nano structures were characterized using surface microscopic techniques. The methanol oxidation activity of the Cu-NDs anode was tested by electrochemical methods in 0.1 M KOH +1 M CH3OH solution and the results were compared with that of bulk Cu as a reference point. The results showed that very well-structured, uniformly and homogeneously distributed Cu-NDs could be fabricated using these combined methods. The peak current density related to methanol oxidation reaction increased and charge transfer resistance reduced almost three times at the Cu-NDs electrode with respect to the bulk Cu. Also, the Cu-NDs electrode has good time stability and high tolerance to COads poisoning. The enhanced activity of the nanostructures was related to good intrinsic activity of Cu for this reaction and their larger available electrochemical active sites. (C) 2019 Hydrogen Energy Publications LLC. Published by Elsevier Ltd. All rights reserved.