The significance of polymer topology to the size and morphology of polymeric assemblies was less studied. Herein we report the preparation of polymersomes with tunable sizes via topological engineering of the solvophobic block of the amphiphilic copolymer in polymerization-induced self-assembly (PISA). The topology of the solvophobic block could be facilely regulated by reversible addition fragmentation chain transfer (RAFT) dispersion copolymerization of two kinds of monomers with distinctive molecular geometries at variable feed ratios. As a proof-of-concept study, RAFT dispersion copolymerization of benzyl methacrylate (BzMA) and stearyl methacrylate (SMA) produced polymersomes with size ranging from 200 to 1500 nm depending on the ratio of BzMA/SMA. Besides vesicles, assemblies with complex internal structures were obtained by varying the ratio of BzMA/SMA, suggesting the robustness of this strategy. The mechanism was revealed by a series of coarse-grained molecular simulations, which elucidated the dependence of the packing parameter on the composition of the solvophobic block. The generality and modularity for regulating vesicular size by topological engineering of solvophobic block were further established by RAFT dispersion copolymerization of BzMA and 2(perfluorooctyl)ethyl methacrylate, which also generated polymersomes with tunable sizes. The topological engineering of copolymer by RAFT dispersion copolymerization thus serves as a versatile and modular approach to controlling the size and morphology of polymer assemblies.