This study examines the trends in air temperature, precipitation and flow rates over a 50-year observation period (1961–2010) and compares two periods, 1961–1985 and 1986–2010. The research was carried out in terms of annual and monthly values. The research area is the Hornad River in Slovakia. The main aim of the study was to examine the evolution of precipitation, air temperature and flows in the Hornad River catchment area, as well as to identify the regions (sub-catchments) most vulnerable to climate change. Increasing trends in air temperature in the years 1961–2010 were found to be statistically significant (the Sen’s slope was between 0.0197 and 0.0239). On the other hand, a statistically significant downward trend in flows was recorded only at the Stratená station (a small mountain catchment, where the Sen’s slope was −0.0063). The remaining upward and downward trends were not statistically significant. Greater differences in the course of the trends were recorded on a monthly basis in individual multi-years. Increasing trends in air temperature were statistically significant from May to August in the period 1961–2010. No trends in precipitation were recorded in the period 1961–2010, and only an upward trend in precipitation was recorded in June from 1986–2010.