AbstractSelf‐reporting fluorescence methods for monitoring folding and aggregation of proteins have a long history in biochemistry. Placing orthogonal luminophores within individual synthetic polymer chains for self‐reporting both folding (i.e., its intramolecular compaction to isolated single‐chain nanoparticles, SCNPs) and unbidden aggregation (i.e., the intermolecular association of SCNPs) remains a great challenge. Herein, a simple and efficient platform to identify both single‐chain compaction and intermolecular aggregation phenomena via photoluminescence is presented based on simultaneous synthesis through Hantzsch ester formation of orthogonal luminophores within the same polymer chain. Starting from non‐luminescent β‐ketoester‐decorated chains, intramolecular compaction is visually detected through fluorescence arising from Hantzsch fluorophores generated as intra‐chain connectors during folding. Complementary, intermolecular association is identified via aggregation‐induced emission (AIE) from orthogonal luminophores displaying intense photoluminescence at redshifted wavelengths after formation of multi‐SCNPs assemblies.