Climate change, through changes in temperature, precipitation, and frequency of extreme events, has influenced agricultural production and food security over the past several decades. In order to assess climate and weather-related risks to fruit and grape production in Serbia, changes in bioclimatic indices and frequency of the occurrence of unfavourable weather events are spatially analysed for the past two decades (1998–2017) and the standard climatological period 1961–1990. Between the two periods, the Winkler and Huglin indices changed into a warmer category in most of the viticultural regions of Serbia. The average change shift was about 200 m towards higher elevations. Regarding the frequency of spring frost, high summer temperatures and water deficit, the most vulnerable regions in terms of fruit and grape production are found alongside large rivers (Danube, Sava, Great and South Morava), as well as in the northern part of the country. Regions below 300 m are under increased risk of high summer temperatures, as the number and duration of occurrences increased significantly over the studied periods. The high-resolution spatial analysis presented here gives an assessment of the climate change influence on the fruit and grapes production. The presented approach may be used in regional impact assessments and national planning of adaptation measures, and it may help increase resilience of agricultural production to climate change.