Covalent organic frameworks (COFs) represent an emerging class of organic photocatalysts. However, their complicated structures lead to indeterminacy about photocatalytic active sites and reaction mechanisms. Herein, we use reticular chemistry to construct a family of isoreticular crystalline hydrazide-based COF photocatalysts, with the optoelectronic properties and local pore characteristics of the COFs modulated using different linkers. The excited state electronic distribution and transport pathways in the COFs are probed using a host of experimental methods and theoretical calculations at a molecular level. One of our developed COFs (denoted as COF-4) exhibits a remarkable excited state electron utilization efficiency and charge transfer properties, achieving a record-high photocatalytic uranium extraction performance of ~6.84 mg/g/day in natural seawater among all techniques reported so far. This study brings a new understanding about the operation of COF-based photocatalysts, guiding the design of improved COF photocatalysts for many applications.