The moisture-dependency of the fracture energy for unmodified and acetylated Scots pine ( Pinus sylvestris L.) and birch ( Betula pendula Roth) has been investigated. Specimens were conditioned at relative humidity levels of 20, 75, and 97%, as well as dry and water-saturated. At moisture contents below 15%, the fracture energy increased with increasing moisture content for both unmodified and acetylated wood, while it decreased for untreated wood at higher moisture contents. A significant difference in moisture-dependency was found, indicating higher fracture energy for unmodified wood compared to acetylated wood at similar moisture contents. Additionally, to assess the impact of the increased brittleness for structural applications, the fracture energy was compared at equal relative humidity levels. The largest difference was seen at 75% relative humidity with approximately 50% lower fracture energy for acetylated wood. No significant differences were found for water-saturated samples. The moisture-dependency of the fracture energy, combined with the reduced hygroscopicity of acetylated wood, is suggested to be one, but not the only, contributing factor to the lower fracture energy of acetylated wood compared to unmodified wood at equal humidity levels. These observations have importance for structural design since design codes often assess material parameters based on ambient humidity.