Thermal spray technology was used to apply a thin layer of copper (Cu metal as an antimicrobial coating) on the surfaces of a number of different solid woods and medium-density fiberboard (MDF) wood composites. The adhesion of a Cu coating to Swietenia macrophylla (mahogany), Quercus (oak), Acer saccharinum (silver maple), Picea (spruce), Pinus strobus (white pine), and MDF was evaluated by a pull-off adhesion test. The resistance of Cu-coated samples to mildew, decay fungi, and water uptake was assessed in the lab. Also, the weathering performance of Cu-coated untreated and heat-treated spruce was evaluated. After proper surface preparation, the adhesion of Cu coatings to hardwood and softwood samples was considered very good, and the adhesion of the Cu coating to MDF was much stronger than the internal bond strength of MDF itself. The Cu coating effectively protected the wood from decay fungi and mildew, while it had no effect on the rate of water absorption and desorption from the wood. After one year of natural weathering in Toronto, Canada, the Cu-coated heat-treated spruce samples had significantly fewer checks than coated, untreated wood. Thermal spray copper coating proved to have the potential to protect wood from biological degradation while also serving as an antimicrobial coating.