The climate transition during the middle Miocene promoted a series of environmental evolutions. However, the response of deep-sea redox conditions to this climate transition remains unclear. Here, we reconstruct the redox conditions in the subtropical Northwest Pacific during the Middle Miocene Climate Transition (MMCT) using the uranium and thorium data from drill cores at different water depths. Our findings indicate that the oxygenation level in the bathypelagic site (U1505) was weak at the early MMCT (14.6–14.1 Ma), elevated at the middle MMCT (14.1–13.3 Ma), and weak again at the late MMCT (13.3–12.8 Ma). In contrast, the oxygenation level in the abyssopelagic site (U1438) was strong in the early MMCT and weak in the middle and late MMCT. Combined with the changes in local productivity and ocean circulation, we argue that the varying oxygenation evolution trends at different water depths are probably related to the change in water mass structure driven by climate cooling from the early to the middle MMCT. However, local export production may be the main controlling factor during the late MMCT. Moreover, the decrease in deep-sea oxygenation across the MMCT also reflects the deepening of the respired carbon pool in the subtropical Northwest Pacific, which possibly contributed to the decline in atmospheric CO2 at that time.