Molybdenum disulfide (MoS2) has emerged as a promising electrocatalyst for catalyzing protons to hydrogen via the so-called hydrogen evolution reaction (HER). In order to enhance the HER activity, tremendous effort has been made to engineer MoS2 catalysts with either more active sites or higher conductivity. However, at present, synergistically structural and electronic modulations for HER still remain challenging. In this work, we demonstrate the successfully synergistic regulations of both structural and electronic benefits by controllable disorder engineering and simultaneous oxygen incorporation in MoS2 catalysts, leading to the dramatically enhanced HER activity. The disordered structure can offer abundant unsaturated sulfur atoms as active sites for HER, while the oxygen incorporation can effectively regulate the electronic structure and further improve the intrinsic conductivity. By means of controllable disorder engineering and oxygen incorporation, an optimized catalyst with a moderate degree of disorder was developed, exhibiting superior activity for electrocatalytic hydrogen evolution. In general, the optimized catalyst exhibits onset overpotential as low as 120 mV, accompanied by extremely large cathodic current density and excellent stability. This work will pave a new pathway for improving the electrocatalytic activity by synergistically structural and electronic modulations.