Edge-sealing, which involves treating the edges of wood products, improves water resistance. This study investigated the feasibility of edge-sealed cross-laminated timber (CLT) panels to reduce capillary water uptake, thereby resisting mould formation. The water and vapour permeabilities of ten characteristically different single-layer sealant coating systems were systematically determined. X-ray computed tomography (CT) scanning methodology was used to enhance detection of material characteristics beyond the standard coating permeability assessment. Moisture content was observed to change during the specimens’ absorption and desorption depending on the sealant system applied. The results revealed different characteristics of coatings during the water absorption and desorption stages. Findings from this study were used to develop recommendations regarding the water resistance of coating systems, curing time, susceptibility to mould formation, and industrial applicability. Results suggest that edge-sealed CLT could minimise the risk of mould formation, which can occur at worksites with minimal weather protection. The method developed in this study provides a basis to evaluate new coating systems and determine which use case is the best for a particular coating type. This study also incorporates insights from industry to identify future research orientations, which may pave the way for new designs and assessment techniques.