In this study, we report a straightforward method to orthogonally functionalise (co)polymers of two independently addressable reactive monomers-the structural analogues 2-isopropenyl-2-oxazoline (iPOx) and 2-vinyl-4,4-dimethyl-5-oxazolone (VDM). Homopolymers were used to identify suitable reaction conditions for their selective post-polymerization modification (PPM) with a range of functional compounds, i.e. thiols, amines, and carboxylic acids, without the addition of any catalysts. Under these optimised conditions, well-defined statistical and block copolymers of iPOx and VDM were orthogonally modified, as confirmed by proton nuclear magnetic resonance spectroscopy, Fourier-transform infrared (FT-IR) and size exclusion chromatography (SEC) measurements. Critically important was the order of functionalisation, with the PPM of the VDM moiety required first to avoid side-reactions. Extending this approach to selective PPM of block copolymers facilitated the preparation of amphiphilic block copolymers consisting of a hydrophilic poly(ethylene glycol) brush block and a hydrophobic terephthalic acid modified block. These modified block polymers were shown to form defined nanostructures in physiological phosphate buffered saline (PBS) solution. Due to its reactivity towards various functional groups available in the majority of natural and synthetic compounds, this copolymer platform provides access to functional polymer libraries with tailored properties.