Analyzing trends in flood magnitude changes and their underlying causes under climate change is a key challenge for the effective management of water resources in arid and semi-arid regions, particularly for inland rivers originating in the Qilian Mountains (QMs). Sen’s slope estimator and Mann-Kendall test were used to investigate spatial and temporal trends in flood magnitude based on the annual maximum peak discharge (AMPD) and Peaks-Over-Threshold (POT3M) flood series of twelve typical rivers from 1970 to 2021. The results showed that in the AMPD series, 42% of the rivers had significantly decreasing trends, while 8% had significantly increasing trends; in the POT3M series, 25% of the rivers had significantly decreasing trends, while 8% had significantly increasing trends. The regional differences in the QMs from east to west were that rivers in the eastern region (e.g., Gulang, Zamu, and Xiying rivers) showed significantly decreasing trends in the AMPD and POT3M series; most rivers in the central region had non-significant trends, while the Shule river in the western region showed a significantly increasing trend. Temperatures and precipitation showed a fluctuating increasing trend after 1987, which were the main factor contributing to the change in flood magnitude trends of the AMPD and POT3M flood series in the QMs. Regional differences in precipitation, precipitation intensity, and the ratio of glacial meltwater in the eastern, central and western regions resulted in the differences in flood magnitude trends between the east and west.