Complementary metal-oxide-semiconductor (CMOS) detectors are a competitive choice for current and upcoming astronomical missions. To understand the performance variations of CMOS detectors in the space environment, we investigate the total ionizing dose effects on custom-made large-format X-ray CMOS detectors. Three CMOS detector samples were irradiated with a Co60 source with a total dose of 70 and 105 krad. We test and compare the performance of these detectors before and after irradiation. After irradiation, the dark current increases by roughly 20∼100 times, and the readout noise increases from 3 e− to 6 e−. The bias level at 50 ms integration time decreases by 13 to 18 digital number (DN) at −30°C. The energy resolution increases from ∼150 to ∼170 eV at 4.5 keV at −30°C. The conversion gain of the detectors varies for <2% after the irradiation. Furthermore, there are about 50 pixels in which bias at 50 ms has changed by more than 20 DN after the exposure to the radiation and about 30 to 140 pixels in which the readout noise has increased by over 20 e− at −30°C at 50 ms integration time. These results demonstrate that the performances of large-format CMOS detectors do not suffer significant degeneration in space environment.