This paper examines the long-term changes in temperature and precipitation in the karst region of Imotski, Croatia, which is of particular interest due to its abundance of karst phenomena. This study analyses temperatures and precipitation on monthly and annual scales at two climatological stations in the region, Imotski and Ričice. Linear regression, the Theil–Sen estimator (β), and the Mann–Kendall test were used to determine the trends and statistical significance. The homogeneity of the data was checked using the Standard Normal Homogeneity Test (SNHT), and the F-test and t-test were used to test the significance of the mean shift between the two subseries. Additionally, the coefficient of variability, standardized rainfall anomaly, and precipitation concentration index were employed to analyze the precipitation variability. The study found a statistically significant (p < 0.05) upward trend in the mean (β = 0.0437) and maximum (β = 0.0590) annual air temperature at the Imotski station and the mean (β = 0.0387) annual temperature at the Ričice station. The SNHT test showed a statistically significant (p < 0.05) shift in the mean annual temperatures after 2007 and maximum annual temperatures after 1998 at the Imotski station. Similarly, a statistically significant (p < 0.05) shift in the mean annual temperatures after 2011 and the maximum annual temperatures after 1998 was found at the Ričice station. A seasonal distribution of precipitation is observed at both the Ričice and Imotski stations, with a downward trend (β = −2.7693) at Ričice and an upward trend (β = 6.0575) at Imotski; however, neither trend is statistically significant (p > 0.05). An increase in the intensity of dry periods and the occurrence of extreme events was also noted. The climatological analysis, conducted for the first time in this area, is a crucial step toward understanding local climate patterns and making informed decisions toward sustainable development and adaptation strategies.