Polymeric biomaterials have many applications including therapeutic delivery vehicles, medical implants and devices, and tissue engineering scaffolds. Both naturally-derived and synthetic materials have successfully been used for these applications in the clinic. However, the increasing complexity of these applications requires materials with advanced properties, especially customizable or tunable materials with bioactivity. To address this issue, there have been recent efforts to better recapitulate the properties of natural materials using synthetic biomaterials composed of sequence-controlled polymers. Sequence control mimics the primary structure found in biopolymers, and in many cases, provides an extra handle for functionality in synthetic polymers. Here, we first review the advances in synthetic methods that have enabled sequence-controlled biomaterials on a relevant scale, and discuss strategies for choosing functional sequences from a biomaterials engineering context. Then, we highlight several recent studies that show strong impact of sequence control on biomaterial properties, including in vitro and in vivo behavior, in the areas of hydrogels, therapeutic materials, and novel applications such as molecular barcodes for medical devices. The role of sequence control in biomaterials properties is an emerging research area, and there remain many opportunities for investigation. Further study of this topic may significantly advance our understanding of bioactive or smart materials, as well as contribute design rules to guide the development of synthetic biomaterials for future applications in tissue engineering and regenerative medicine.