Fabrication of biocompatible core-shell microcapsules in a controllable and scalable manner remains an important but challenging task. Here, we develop a one-step microfluidic approach for the high-throughput production of biocompatible microcapsules, which utilizes single emulsions as templates and controls the precipitation of biocompatible polymer at the water/oil interface. The facile method enables the loading of various oils in the core and the enhancement of polymer shell strength by polyelectrolyte coating. The resulting microcapsules have the advantages of controllability, scalability, biocompatibility, high encapsulation efficiency and high loading capacity. The core-shell microcapsules are ideal delivery vehicles for programmable active release and various controlled release mechanisms are demonstrated, including burst release by vigorous shaking, pH-triggered release for targeted intestinal release and sustained release of perfume over a long period of time. The utility of our technique paves the way for practical applications of core-shell microcapsules.