The U.S. State of California has experienced frequent drought events, hotter temperatures and other disruptions to the climate system whose effects on ecosystems have been widely reported in recent decades. Studies primarily confined to specific vegetation communities or species, individual drought incidents, or analysis over a relatively short intervals, has limited our understanding of the broad-scale effects on tree cover and the spatiotemporal variability of effects across broader regions. We focused analysis on multi-annual land cover and land surface change to assess patterns and trends in tree cover loss in tree-dominated Californian ecoregions from 1986 to 2019. The top three years of total tree cover loss for the state were 2018 (1901 km²), 2015 (1556 km²), and 2008 (1549 km²). Overall, annual tree cover loss had upward trends. Tree cover loss rapidly surged later in the study period and was apparently driven by climate stress and wildfires. Underlying geographic variability was apparent in both non-fire and fire-related tree cover loss that sharply increased during hotter multi-year droughts. The increasingly hotter and drier climate conditions were associated with significant increases in fire-induced mortality. Our findings indicate that a possible effect of future hotter and drier climate would lead to further tree cover loss, thereby endangering California's ecosystem goods and services. Geographic variability in tree cover trends indicates that ecoregion-specific mitigation and adaptation strategies would be useful to conserve the region's forest resources. Such strategies may benefit from consideration of historical disturbances, ecoregion's sensitivity to disturbance types, as well as potential ecoregion-specific climate-vegetation-fire feedbacks.