Central Europe is not a typical wildfire region; however, an increasingly warm and dry climate and model-based projections indicate that the number of forest fires are increasing. This study provides new insights into the drivers of forest fire occurrence in the Czech Republic, during the period 2006 to 2015, by focusing on climate, land cover, and human activity factors. The average annual number of forest fires during the study period was 728, with a median burned area of 0.01 ha. Forest fire incidence showed distinct spring (April) and summer (July to August) peaks, with median burned areas of 0.04 ha and 0.005 ha, respectively. Relationships between the predictors (climate data, forest-related data, socioeconomic data, and landscape-context data) and the number of forest fires in individual municipality districts were analyzed using Generalized Additive Models (GAM) on three time scales (annually, monthly, and during the summer season). The constructed GAMs explained 48.7 and 53.8% of forest fire variability when fire occurrence was analyzed on a monthly scale and during the summer season, respectively. On an annual scale, the models explained 71.4% of the observed forest fire variability. The number of forest fires was related to the number of residents and overnight tourists in the area. The effect of climate was manifested on monthly and summer season scales only, with warmer and drier conditions associated with higher forest fire frequency. A higher proportion of conifers and the length of the wildland–urban interface were also positively associated with forest fire occurrence. Forest fire occurrence was influenced by a combination of climatic, forest-related, and social activity factors. The effect of climate was most pronounced on a monthly scale, corresponding with the presence of two distinct seasonal peaks of forest fire occurrence. The significant effect of factors related to human activity suggests that measures to increase public awareness about fire risk and targeted activity regulation are essential in controlling the risk of fire occurrence in Central Europe. An increasing frequency of fire-conducive weather, forest structure transformations due to excessive tree mortality, and changing patterns of human activity on the landscape require permanent monitoring and assessment of possible shifts in forest fire risk.