The DNA-guided assembly of biohybrid sequence-defined poly(phosphodiester)s was investigated. These polymers contain long non-natural segments covalently connected to single-stranded DNA sequences. These biohybrid structures were synthesized by automated phosphoramidite chemistry using both nucleoside and abiological phosphoramidite monomers. Using complementary DNA strands, the precursors were then assembled in aqueous buffer into linear or star-like superstructures. For instance, linear supramolecules containing 442 (352 non-natural monomers connected by three double-stranded DNA bridges of 15 base pairs) and 990 monomers (720 non-natural monomers connected by nine double-stranded DNA bridges of 15 base pairs) were prepared. A four-arm star structure containing 488 monomers (352 non-natural monomers connected by a four-arm junction of 68 base pairs) was also achieved. The formed supramolecules were characterized by electrophoresis, UV spectroscopy, and atomic force microscopy. All these techniques evidenced the formation of the expected supramolecules, although some defects were also evidenced. These results open up interesting avenues for the design of two-dimensional (2D) and three-dimensional (3D) constructs based on informational poly(phosphodiester)s.