Metal-organic frameworks (MOFs) are known for their specific interactions with gas molecules; this, combined with their rich and ordered porosity, makes them promising candidates for the photocatalytic conversion of gas molecules to useful products. However, attempts to use MOFs or MOF-based composites for CO photoreduction usually result in far lower CO conversion efficiency than that obtained from state-of-the-art solid-state or molecular catalysts, even when facilitated by sacrificial reagents. Here we create 'molecular compartments' inside MOF crystals by growing TiO inside different pores of a chromium terephthalate-based MOF (MIL-101) and its derivatives. This allows for synergy between the light-absorbing/electron-generating TiO units and the catalytic metal clusters in the backbones of MOFs, and therefore facilitates photocatalytic CO reduction, concurrent with production of O. An apparent quantum efficiency for CO photoreduction of 11.3 per cent at a wavelength of 350 nanometres is observed in a composite that consists of 42 per cent TiO in a MIL-101 derivative, namely, 42%-TiO-in-MIL-101-Cr-NO. TiO units in one type of compartment in this composite are estimated to be 44 times more active than those in the other type, underlining the role of precise positioning of TiO in this system.