The　synthesis　and　characterization　of　an　FeII/FeIII　metal-organic　framework　(MOF)　nanocrystal　with　spatial　heterogeneity　that　arises　from　the　non-uniform　distribution　of　different　valence　states　is　disclosed.　The　FeII/FeIII-Ni　Prussian　blue　analog　(PBA)　delivers　superior　photocatalytic　performance　in　the　selective　CO2　reduction　reaction　thanks　to　the　strong　FeII/FeIII　coupling,　with　CO　yield　up　to　12.27 mmol　g−1　h−1　and　90.6%　selectivity　under　visible-light　irradiation.　Density　functional　theory　calculation　and　experimental　studies　prove　that　the　spatial　heterogeneity　of　FeII/FeIII　in　the　individual　MOF　nanocrystal　not　only　directs　and　expedites　the　charge　transfer　within　a　catalyst　particle　but　also　creates　the　heterogeneity　of　catalytically-active　Ni　sites　for　efficient　CO2　photoreduction.　The　current　findings　add　to　a　growing　literature　of　materials　with　compositional　heterogeneity　and　provide　a　reference　for　future　research.　©　2023　Wiley-VCH　GmbH.