Generation of robust, well-defined chemical contrast patterns at desired resolution is of critical importance for applications such as biological assays for sensing and diagnostics, surfaces for cell adhesion and growth, directed self-assembly of block copolymers, site-specific immobilization of nanoscale objects such as DNA origami nanostructures and gold nanoparticles. In particular, leveraging different polymer brushes to modify the corresponding lithographically defined regions is a common strategy to generate chemical contrast nanopatterns, where the effects from potential brush interpenetration could be minimized by molecular weight engineering per specific application requirements. With a sequence-defined polymer brush platform, the parameter space of chemical contrast nanopatterns can be further expanded with precise, monomer-level engineering of chemical functionalities.