Climate change has influenced the discharge regime of rivers during the past decades. This study aims to reveal climate-induced interannual trends of average annual discharge and discharge maxima in a Mediterranean river from 1981 to 2017. To this aim, the Pinios river basin was selected as the study area because it is one of the most productive agricultural areas of Greece. Due to a lack of sufficient measurements, simulated daily discharges for three upstream sub-basins were used. The discharge trend analysis was based on a multi-faceted approach using Mann-Kendall tests, Quantile-Kendall plots, and generalized additive models (GAMs) for fitting non-linear interannual trends. The methodological approach proposed can be applied anywhere to investigate climate change effects. The results indicated that the average annual discharge in the three upstream sub-basins decreased in the 1980s, reaching a minimum in the early 1990s, and then increased from the middle 1990s to 2017, reaching approximately the discharge levels of the early 1980s. A more in-depth analysis unraveled that the discharge maxima in September were characterized by statistically significant increasing interannual trends for two of the three sub-basins. These two sub-basins are anthropogenically low affected, thus highlighting the clear impact of climate change that may have critical socioeconomic implications in the Pinios basin.