Macromolecular architecture is a key factor determining the materials properties of polymers. Exploration of novel structural arrangements has become a viable means to develop advanced functional nanomaterials. Recent developments in polymer chemistry have forged robust synthetic platforms for innovative polymeric materials with highly regulated structures, functionalities, and compositions. This review summarizes the latest synthetic strategies for well-defined polymer architectures through covalent chemistry, with the focus on four main types of well-defined macromolecular constructs.