Grain prices in early modern Europe reflected the effects of weather and climate on crop yields and a complex array of societal and socio-economic factors. This study presents a newly developed series of grain prices for Sušice (southwestern Bohemia, Czech Republic) for the period 1725–1824 CE, based on various archival sources. It aims to analyse their relationships with weather and climate, represented by temperature, precipitation, and drought (self-calibrated Palmer Drought Severity Index, scPDSI) reconstructions, as well as particular weather extremes and anomalies reported in documentary evidence. Wheat, rye, barley, and oats series in Sušice showed high mutual correlations. The mean highest prices during the year typically occurred from May to July before the harvest, while prices usually declined afterwards. Wheat, rye, and barley prices were significantly negatively correlated with spring temperatures and positively correlated with scPDSI from winter to summer. This indicates that wetter winters, cooler and wetter springs, and wetter summers contributed to higher prices. The extremely high grain prices in the years 1746, 1771–1772, 1802–1806, and 1816–1817 were separately analysed with respect to weather and climate patterns and other socio-economic and political factors. The results obtained were discussed in relation to data uncertainty, factors influencing grain prices, and the broader European context.