CO2injection has been proved to be the most promising enhanced oil recovery (EOR) method for shale reservoirs. Water bridges impeding oil flow in shale nanopores have a significant impact on CO2-EOR, and the microscopic mechanism of this effect is still unclear, seriously hindering the design of CO2injection technologies. In this work, molecular dynamics simulations were employed to study the microscopic process of fluid transport following CO2injection into shale nanopores where oil and a water bridge coexist. Our results confirm that CO2can break through the water bridge in shale nanopores to form fluid channels and improve the mobility and recovery of crude oil. The whole process can be divided into three stages: (i) CO2diffuses into the nanopore, while oil diffuses into the fracture under concentration gradient; (ii) CO2breaks through the water bridge; and (iii) CO2drives oil out of the nanopore under a pressure gradient. Furthermore, four major microscopic mechanisms of CO2breaking through a water bridge are summarized: (i) “porous” distribution of water molecules in the water bridge; (ii) less and weaker hydrogen bonds in the center of the water bridge; (iii) CO2flushing the water bridge; and (iv) CO2dragging water molecules through hydrogen bonding. Finally, the total oil recovery factor keeps increasing in the synergy of pressure flooding and interdiffusion of CO2and oil. It is worth noting that CO2injection and shut-in need to be properly regulated to avoid the reinjection of recovered oil into the nanopore owing to continuous pressure flooding. CO2injection induces the swelling of oil and increases the mobility of oil, which can be further enhanced after the breakthrough of the water bridge. Our results advance the understanding of the microscopic mechanism of CO2-EOR of water-bearing shale reservoirs and the exploitation of unconventional resources.