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Climate change, variability and anthropogenic forcings such as land use change are the main forcings of river discharge variability. However, an understanding of their simultaneous impacts on river discharge remains limited in some parts of the world. To shed light on this issue, the objective of this article is to investigate the effects of rainfall variability and land use change on river discharge in the Nyong basin (at Olama and Mbalmayo gauging stations) and some of its sub-basins (So’o and Mefou) over the long period 1950–2018. To achieve this goal, hydro-meteorological data of the Nyong basin and sub-basins were analyzed using the Pettitt test. Likewise, land use changes in the basin and sub-basins were also analyzed using supervised classifications of Landsat satellite images of the basins at different periods (1973, 2000 and 2018). On the annual scale, rainfall has decreased statistically over the studied basins. In the large basins (Olama and Mbalmayo), this decrease in rainfall is synchronous with that of discharges, while it is concomitant with an increase in the Mefou (small basin). After the ruptures within time series identified in the annual modules, the extreme discharges (maximum and minimum) decreased in Olama; in Mbalmayo, the maximum discharges remained stable while the minimum discharges decreased. On the other hand, the maximum and minimum discharges have significantly increased in the Mefou. The stability of maximum discharges at Mbalmayo and the increase in extremes on the Mefou in a context where the precipitation that generates the discharge has decreased can be attributed to land use change. These changes are essentially marked by an increase in impervious areas and a reduction in forest cover. On the seasonal scale, the impact of precipitation in the dry season is visible on the flows of the rainy seasons that follow them on the large basins (Olama and Mbalmayo). Between the decades 1970–1990 and 2000–2010, there was respectively a significant increase, then a decrease in summer precipitation, which impacted the autumn discharges in the same direction. Conversely, between the same intervals, there was a significant decrease, then a slight increase in winter precipitation. The impact of winter precipitation on the spring discharge is more visible during the first period only (1970–1990). During the second period, winter precipitation seems to have more of an impact on the runoff for the same season. In the Mefou sub-basin, the precipitation plays an essentially amplifying role in the increase in discharge in the seasons during which they occur. Those having experienced an increase, or a maintenance of precipitation (summer and spring) recorded the most significant increases in discharges. These results could be useful for long-term planning on the demand and use of water, as well as flood management in the basins