Photocatalytic oxygen reduction reactions and water oxidation reactions are extremely promising green approaches for massive HO production. Nonetheless, constructing effective photocatalysts for HO generation is critical and still challenging. Since the network topology has significant impacts on the electronic properties of two dimensional (2D) polymers, herein, for the first time, we regulated the HO photosynthetic activity of 2D covalent organic frameworks (COFs) by topology. Through designing the linking sites of the monomers, we synthesized a pair of novel COFs with similar chemical components on the backbones but distinct topologies. Without sacrificial agents, TBD-COF with cpt topology exhibited superior HO photoproduction performance (6085 and 5448 μmol g h in O and air) than TBC-COF with hcb topology through the O-O⋅-HO, O-O⋅-O -HO, and HO-HO three paths. Further experimental and theoretical investigations confirmed that during the HO photosynthetic process, the charge carrier separation efficiency, O⋅ generation and conversion, and the energy barrier of the rate determination steps in the three channels, related to the formation of *OOH, *O , and *OH, can be well tuned by the topology of COFs. The current study enlightens the fabrication of high-performance photocatalysts for HO production by topological structure modulation.