Topological defects, the fundamental entities arising from symmetry-breaking, have captivated the attention of physicists, mathematicians, and materials scientists for decades. Here we propose and demonstrate a novel method for robust control of topological defects in a liquid crystal (LC), an ideal testbed for the investigation of topological defects. A liquid layer is introduced on the LC in microwells in a microfluidic device. The liquid/LC interface facilitates the control of the LC alignment thereby introducing different molecules in the liquid/LC phase. A topological defect is robustly formed in a microwell when the liquid/LC interface and the microwell surface impose planar and homeotropic alignment, respectively. We also demonstrate the formation/disappearance of topological defects by light illumination, realized by dissolving photo-responsive molecules in the LC. Our platform that facilitates the control of LC topological defects by the introduction of different molecules and external stimuli could have potential for sensor applications.