The Middle Volga Region is one of the most populated and agriculturally developed geographic regions of the East European Plain within European Russia, where noticeable changes in climate and land use/cover were observed since the 1980s and the early 1990s respectively. The long-term year-to-year (trend) variability (during mainly 1960–2016) in water flow and suspended sediment yield of 14 small and medium-size rivers in the Middle Volga Region was analyzed in the paper. It is shown that in all the studied rivers there was a statistically significant decrease (on average, by 77.2 ± 4.5%) in the intra-annual irregularity of the water flow between 1960–1979 (as a baseline period) and 2002–2016 (the period of the greatest relative climate change in the region). This decrease was caused by a statistically significant reduction in the water flow during the snowmelt period (on average, by 37.4 ± 9.8%) and by an increase in the water flow during the low-water (baseflow) seasons – during the winter months (by 145.2 ± 57.6%) and the river-ice-free period (by 94.9 ± 39.7%). The intensity of snowmelt-induced flood flow has also statistically significantly decreased (by 40.4 ± 8.2%). At the same time, a reduction in the river suspended sediment yield was more significant – by 27.9 ± 26.9 times; it was the result of great changes in soil/rill/gully erosion intensity in the region. This reduction is confirmed by an analysis of sedimentation rates within one of the small (dry valley) catchments in the north of the studied region over the past 60 years. The changes in climate (chiefly a decrease in the depth of freezing of the soil during the snowmelt period, mainly April) and land use/cover, associated basically with reduction in cultivated land area (especially in the 1990s, after the collapse of the Soviet Union), are considered to be as the main reasons for the aforementioned trends that were characteristic in general for almost the entire southern half of European Russia.