A first-time common cross-border assessment of observed climatic changes in the Saxon–Bohemian region was the aim of the German–Czech climate cooperation INTERKLIM. This paper focuses on the observed changes of temperature and precipitation averages and extremes within the period 1961–2010, investigating how variations of a range of climate indices were regionally shaped by changes in frequency and character of weather types. This investigation serves to enhance our understanding of the regional climate characteristics to develop transboundary adaptation strategies and focuses on the classification of the “Grosswetterlagen” using the parameters of air temperature and precipitation. Climate data were quality controlled and homogenized by a wide range of methods using the ProClimDB software with a subsequent comprehensive regional visualization based on Geographical Information Systems. Trends for the temperature averages showed increasing trend values mainly from January to August, especially for high temperature extremes. Precipitation trends displayed regionally varying signals, but a strong spatially uniform decrease from April to June (early growing season) and a distinctive increase from July to September (late growing season). Climatic changes were supported by frequency changes of weather types, e.g., the drying from April to June was related to a decrease/increase in patterns causing rather wet/dry conditions, while from July to September opposite trends were observed. Our results represent regional climatic changes in a complex topography and their dependency on variations in atmospheric circulation peculiarities.