The West Morava (WM) River, situated in Serbia’s Central region, boasts the largest reservoir of freshwater resources within the country. The primary objective of this study was to investigate alterations in the flow (Q) of the WM River (length of 308 km) at the Jasika hydrological station (near the confluence) spanning from 1948 to 2023. Trend analyses and standardized deviation method across monthly, seasonal, and annual timeframes indicates an overall shift towards “drier” conditions along the river’s trajectory. When examining the analysis at a daily level, utilizing the percentile method revealed a diminishing trend in the annual count of days small waters (Qd<9th), very small waters (Qd<25th), large waters (Qd>75th), and very large waters (Qd>91st). However, in the current segment of the 21st century (2001–2023), there has been a notable rise in the risk of floods, evidenced by a significant increase in the annual count of days with Qd>91st. It’s worth noting that river flow is chiefly influenced by precipitation (P) and air temperature (T), which in turn impacts evaporation rates. The findings from the Pearson correlation coefficient analysis indicate that several atmospheric oscillations, including NAO, NAO-500, NCP, AO, MO1, MO2, WeMO, and EAWR, exert a significant influence on the local hydroclimate conditions, particularly during colder months. Additionally, SNAO and AMO exhibit substantial impact during the summer period. Notably, the influence of EA is pronounced on T during February, April, and August, with correlation coefficients ranging between 0.61–0.71. Conversely, the connections with ENSO, SOI, SCAND, and POLEUR appear to be comparatively weaker overall. Given the crucial importance of the WM River for Serbia, it is necessary to define as soon as possible certain plans related to flow equalization and sustainable management of water resources, but also mitigation and adaptation to current and specially projected future climate changes.