Wood is an increasingly important material in the sustainable transition of societies worldwide. The performance of wood in structures is intimately tied to the presence of moisture in the material, which directly affects important characteristics such as dimensions and mechanical properties, and indirectly its susceptibility to fungal decomposition. By chemical modification, the durability of wood in outdoor environments can be improved by reducing the amount of moisture present. In this study, we refined a well-known chemical modification with acetic anhydride and showed how the spatial distribution of the modification of Norway spruce (Picea abies (L.) Karst.) could be controlled with the aim of altering the wood-water interactions differently in different parts of the wood structure. By controlling the reaction conditions of the acetylation it was possible to acetylate only the cell wall-lumen interface, or uniformly modify the whole cell wall to different degrees. The spatial distribution of the acetylation was visualised by confocal Raman microspectroscopy. The results showed that by this targeted acetylation procedure it was possible to independently alter the wood-water interactions in and outside of cell walls. The cell wall-lumen interface modification altered the interaction between the wood and the water in cell lumina without affecting the interaction with water in cell walls while the uniform modification affected both. This opens up a novel path for studying wood-water interactions in very moist environments and how moisture distribution within the wood affects its susceptibility towards fungal decomposition.