The lower Neretva river basin includes a fertile valley at the estuary into the Adriatic Sea, where intense agricultural production occurs, and the higher terrain where drinking water resources exist. To provide input for the further assessment of crop-yield production and hydrological risks, climate and climate change were analysed using the Opuzen station air temperature and total precipitation data for the 1961–2015 period. Both historical and future climates (2021–2050) were assessed based on simulations of three regional climate models (RCMs). The RCMs were forced by the observed concentrations of greenhouse gases (GHGs) from 1951 to 2000, and the IPCC A1B scenario of the GHG emissions was applied from 2001 onwards. The models were compared with the observations, and two bias adjustment methods were evaluated. The results generally showed a significant increase in the mean annual and seasonal temperature and a weak decreasing trend in annual and seasonal precipitation. Projections revealed a predominant increase in the mean temperature by the mid-21st century for all three RCMs (between 0.5 and 3.5 °C). The precipitation changed by between −60 and +60% throughout the year for the different models, although the changes generally were not statistically significant.