Large wildfires in California cause significant socioecological impacts, and half of the federal funds for fire suppression are spent each year in California. Future fire activity is projected to increase with climate change, but predictions are uncertain because humans can modulate or even override climatic effects on fire activity. Here we test the hypothesis that changes in socioecological systems from the Native American to the current period drove shifts in fire activity and modulated fire-climate relationships in the Sierra Nevada. We developed a 415-y record (1600-2015 CE) of fire activity by merging a treering-based record of Sierra Nevada fire history with a 20th-century record based on annual area burned. Large shifts in the fire record corresponded with socioecological change, and not climate change, and socioecological conditions amplified and buffered fire response to climate. Fire activity was highest and fire-climate relationships were strongest after Native American depopulation-following mission establishment (ca. 1775 CE)-reduced the self-limiting effect of Native American burns on fire spread. With the Gold Rush and EuroAmerican settlement (ca. 1865 CE), fire activity declined, and the strong multidecadal relationship between temperature and fire decayed and then disappeared after implementation of fire suppression (ca. 1904 CE). The amplification and buffering of fire-climate relationships by humans underscores the need for parameterizing thresholds of human-vs. climate-driven fire activity to improve the skill and value of fire-climate models for addressing the increasing fire risk in California.anthropogenic landscapes | fire ecology | land use | regime shifts | climate variability A n increase in the extent of forest fires in the American West since the mid-1980s (1) has enhanced risks to lives, property, water quality, biodiversity, carbon sequestration, and other ecosystem services (2). This increasing wildfire trend has become even steeper during the past decade, with a higher number of large wildfires (>100 km 2 ) each year in each Western state compared with the annual average from 1980 to 2000 (3). The fire problem is particularly acute in California, where a history of fire suppression (4), climate change (1, 5), more extreme fire weather (6), expanding development (7), and massive wildfires (e.g., 2013 Rim Fire, 1,042 km 2 ) have caused significant socioecological impacts. Future area burned in California is projected to further increase with anthropogenic warming (8). With more than half of the annual federal firefighting budget already being spent suppressing fires in California (4), a sustainable system of fire management requires approaches beyond active fire suppression (9). Predicting future fire activity is challenging because humans can alter fire regimes and fire-climate relationships even if climate becomes more conducive to fire (10). Changes in socioecological systems (SESs) can modulate or even override climatic effects on fire regimes through changing land use, igniti...