Monolayer molybdenum disulfide (MoS2) has attracted great interest due to its potential applications in electronics and optoelectronics. Ideally, single-crystal growth over a large area is necessary to preserve its intrinsic figure of merit but is very challenging to achieve. Here, we report an oxygen-assisted chemical vapor deposition method for growth of single-crystal monolayer MoS2. We found that the growth of MoS2 domains can be greatly improved by introducing a small amount of oxygen into the growth environment. Triangular monolayer MoS2 domains can be achieved with sizes up to ∼350 μm and a room-temperature mobility up to ∼90 cm(2)/(V·s) on SiO2. The role of oxygen is not only to effectively prevent the poisoning of precursors but also to eliminate defects during the growth. Our work provides an advanced method for high-quality single-crystal monolayer MoS2 growth.