Under the impact of global climate change, the ongoing alterations in meteorological and large-scale climatic factors which drive hydrological processes present significant challenges to water resources management and allocation. As the largest watershed of Poyang Lake, the Ganjiang River Basin plays a crucial role in the frequent occurrences of droughts and floods in Poyang Lake in recent years. This study analyzes the runoff trends in the Ganjiang River Basin using daily meteorological data and daily runoff data from the Waizhou Hydrological Station located at the basin’s outlet, covering the period from 1966 to 2020. Employing the Mann-Kendall trend test, Geodetector, and wavelet analysis, we investigate the trends in runoff, the explanatory power of meteorological factors on runoff, and the variability and teleconnections between the monthly average flow of the Ganjiang River Basin, the Atlantic multidecadal oscillation (AMO) and El Nio-southern oscillation (ENSO). The results reveal that the runoff in this basin exhibits an insignificant upward trend, likely due to the interactions between the non-significant increase in precipitation and other meteorological factors. Precipitation emerges as the dominant factor influencing runoff, with an explanatory power of up to 0.827 on the annual scale. The interaction of multiple factors provides a more significant explanatory power than the simple sum of any two individual factors. The influence of AMO on runoff is mainly observed in the 4-year cycle, while ENSO shows a better correspondence with approximate 2-year cycles.