We present the first stable isotope (δ13C and δ18O) speleothem record from continental Croatia retrieved from two coeval stalagmites from Nova Grgosova Cave. U-Th dates constrain the stalagmite growth history from 10 ka to the present, revealing coeval growth between 7.8 and 5.6 ka. We interpret δ18O as an autumn/winter hydrological proxy related to changes of vapor source, precipitation amount, and/or seasonal rainfall distribution, while δ13C predominantly responds to spring/summer vegetation status and soil microbial activity. We identify several centennial to millennial-scale hydroclimate oscillations during this period that result from multiple forcing factors. Along with amount and source effect, it appears that some centennial variations were governed also by seasonal moisture balance. From 9.2 to 8.8 ka BP, the local environmental setting was characterized by enhanced vegetation activity, while during the 8.2 ka event the main feature was a change in precipitation seasonality. The most prominent change, identified in both δ13C records, is a sudden decline of vegetation and soil biological activity around 7.4 ka, indicating a precipitation decrease at a time of maximum plant growth in spring and summer and likely also reduced precipitation in autumn and winter. Although small in magnitude in these speleothems, a peak in δ18O and δ13C values at 4.3–4.1 ka suggests that both summer and winter conditions were substantially drier during the 4.2 ka event, in accordance with increased Mediterranean aridity and consistent with other global climate changes reported at this time. Compared to the present North Atlantic Oscillation (NAO) influence, we assume that millennial Holocene NAO-like variations were persistent through the Holocene via their effect on modifying local/regional air temperature, vapor origin, and inter- and intrannual precipitation distribution. Anthropogenic deforestation, which was the first major human impact on the environment during the Neolithic agricultural revolution, is excluded as a leading factor in δ13C variability since the first sedentary settlements were established further to the east in more arable locations along river valleys. However, the impact of intensive mining around the cave site during the last millennium is evident, with substantial deforestation driving an increase in δ13C.