The incidence of cardiopulmonary vascular diseases is extremely high and mechanic stress plays an important role in vascular remodeling. Reactive oxygen species (ROS) at physiological levels modulate cell signaling while excessiveROS trigger oxidative stress and induce injury. The types of mechanical stresses in the vascular system and the sources of ROS were summarized. Besides, the roles and mechanisms of mechanical stress-induced oxidative stress in cardiopulmonary vascular diseases were discussed. This review will facilitate a deeper understanding of vascular activity and disease development at the molecular level, provide potential targets for treating vascular diseases. In addition, there are still research gaps on the mechanism of oxidative stress induced by mechanical stress in vascular diseases. Therefore, the potential research direction of mechanical stress-induced oxidative stress in the cardiopulmonary vascular system is also predicted, which may promote the development of mechanobiology to a certain extent.