The conducted research is of particular importance for the country’s food security in the context of climate change in Southeastern Poland. The aim of the research was to determine the influence of climate on the variability of the appearance and the rate of spread of potato blights as the main factor limiting the potato yield in the conditions of Central and Eastern Europe. Combined statistical and simulation modeling methods were used. A mixed effect model was used to detect the effects of temperature, humidity, rainfall and wind speed on potato yield, and partial regression analysis models were used. The natural, agricultural and economic conditions in terms of suitability for potato cultivation were assessed, and factors influencing the fluctuation of the cultivated acreage, yield and harvesting of potatoes were identified. The forecast was based on empirical data from 2000 to 2019. It has been proven that potato cultivation in Southeastern Poland is more vulnerable to climate change than in the rest of the country. The results obtained from analyzing multi-annual results can help policymakers to develop strategies to increase the stability of future potato production and the safety of the crop. This will enable the better use of generated data and methodological approaches to analyze the role of climate, both on a regional and global scale.