The development of an active, earth-abundant, and inexpensive catalyst for the oxygen evolution reaction (OER) is highly desirable but remains a great challenge. Here, by combining experiments and first-principles calculations, we demonstrate that MoS2 quantum dots (MSQDs) are efficient materials for the OER. We use a simple route for the synthesis of MSQDs from a single precursor in aqueous medium, avoiding the formation of unwanted carbon quantum dots (CQDs). The as-synthesized MSQDs exhibit higher OER activity with a lower Tafel slope in comparison to that for the state of the art catalyst IrO2/C. The potential cycling of the MSQDs activates the surface and improves the OER catalytic properties. Density functional theory calculations reveal that MSQD vertices are reactive and the vacancies at the edges also promote the reaction, which indicates that the small flakes with defects at the edges are efficient for the OER. The presence of CQDs affects the adsorption of reaction intermediates and dramatically suppresses the OER performance of the MSQDs. Our theoretical and experimental findings provide important insights into the synthesis process of MSQDs and their catalytic properties and suggest promising routes to tailoring the performance of the catalysts for OER applications.