A closed-loop, autonomous molecular discovery platform driven by integrated machine learning tools was developed to accelerate the design of molecules with desired properties. We demonstrated two case studies on dye-like molecules, targeting absorption wavelength, lipophilicity, and photooxidative stability. In the first study, the platform experimentally realized 294 unreported molecules across three automatic iterations of molecular design-make-test-analyze cycles while exploring the structure-function space of four rarely reported scaffolds. In each iteration, the property prediction models that guided exploration learned the structure-property space of diverse scaffold derivatives, which were realized with multistep syntheses and a variety of reactions. The second study exploited property models trained on the explored chemical space and previously reported molecules to discover nine top-performing molecules within a lightly explored structure-property space.