The distributions of physicochemical property values, like the octanol-water partition coefficient, are routinely calculated to describe and compare virtual chemical libraries. Traditionally, these distributions are derived by processing each member of a library individually and summarizing all values in a distribution. This process becomes impractical when operating on chemical spaces which surpass billions of compounds in size. In this work, we present a novel algorithmic method called SpaceProp for the property distribution calculation of large nonenumerable combinatorial fragment spaces. The novel method follows a combinatorial approach and is able to calculate physicochemical property distributions of prominent spaces like Enamine's REAL Space, WuXi's GalaXi Space, and OTAVA's CHEMriya Space for the first time. Furthermore, we present a first approach of optimizing property distributions directly in combinatorial fragment spaces.