This manuscript reports on the modulation of the photoreactivity of a series of chromones, also known as benzo-γ-pyrones, by absorption into a porous self-assembled host formed from phenylethynylene bis-urea macrocycles. Chromone and four derivatives namely 6-fluorochromone, 6-bromochromone, 7-hydroxy-4-chromone, and 3-cyanochromone are unreactive in the solid-state. Each of these derivatives was loaded into the nanochannels of self-assembled phenylethynylene bis-urea macrocycles to form solid host·guest complexes, which were subsequently UV-irradiated at room temperature under argon atmosphere. We observed that chromone and 6-fluorochromone underwent selective [2 + 2] photodimerization reactions to produce anti-HT dimers in high selectivity and conversion. The 6-bromochromone also reacted in high selectivity and conversion to afford an aryl coupling adduct. In each case, the products were extracted, and the crystalline host recovered. In comparison, 7-hydroxy-4-chromone, and 3-cyanochromone were unreactive within the complex. Simple GCMC simulation studies suggest that chromone, 6-fluorochromone, and 6-bromochromone were loaded in orientations that facilitate photoreaction, and correctly predicted that the anti-HT dimer would be favored in the chromone case. In contrast, syn-HH dimers were predicted by GCMC simulations for the halogen containing derivatives but were not observed. The simulations with 7-hydroxy-4-chromone were in agreement with the observed reactivity. We compare these computational and experimental findings and suggest future methods for optimizing simulation parameters. Our goal is to expand the scope and accuracy of the simulations to be able to predict the reactivity of guests encapsulated within columnar nanotubes.