A convenient method was reported to control the topological structure of copolyphosphates by adjusting the pendant group of cyclic phosphate monomers (CPMs) in the ring-opening polymerization (ROP), including linear block, star block, and hyperbranched multiarm structure. Linear block copolyphosphate (PEP-b-PIPP) was prepared by a two-step ROP procedure of CPMs with different pedant groups, i.e., monofunctional propargyl alcohol first initiated the ROP of the CPM with ethyl and then the CPM with isopropyl in turn. Similarly, star block copolyphosphate (SPEP-b-PIPP) was also synthesized when the monofunctional propargyl alcohol was replaced by a trifunctional trimethylolpropane. When the pendant group of CPM was changed into 2-hydroxyethyl, hyperbranched polyphosphate (HPHEP) was obtained first through the self-condensing ring-opening polymerization (SCROP) of such CPM, and then the terminal hydroxyls of HPHEP further initiated the ROP of CPM with ethyl to produce hyperbranched multiarm copolyphosphate (HPHEP-star-PEP). The resulting copolyphosphates were characterized by NMR, GPC, FTIR, and DSC techniques in detail, and the results confirmed their topological structures. Moreover, methyltetrazolium assay and AO/EB double staining methods indicated that all copolyphosphates with different topological structures had excellent biocompatibility against NIH 3T3 cells and would be applied as novel biomedical materials.