Creating molecular networks with different topologies using identical molecular linkers is fundamentally important, but requires a precise chemistry control. Here, we propose an effective strategy to regulate network topologies of two-dimensional (2D) covalent organic frameworks (COFs) through conformation switching of molecular linkages. By simply altering the substituents of an identical molecular linker, the topology-selective synthesis of two highly crys-talline 2D COFs can be readily achieved. Their distinct crystal structures are observed and determined by low-dose high-resolution transmission electron microscopy imaging, indicating that the driving force for linkage conformation switching is intramolecular hydrogen bonding. Our strategy would greatly diversify the COF topologies and enable vast post-synthetic modifications like boron complexation, endowing these structures with unique optical property, such as fluorescence “turn on” and “aggregation-induced emission”.