The hemi-boreal zone, marking North America’s southern boreal forest boundary, has evolved post-glaciation, hosting diverse ecosystems including mixed forests with savannas, grasslands, and wetlands. While human, climate, and fire interactions shape vegetation dynamics therein, specific influences remain unclear. Here we unveil 12,000 years of hemi-boreal zone dynamics, exploring wildfire, vegetation, climate, and human population size interactions at such long time scales. Postglacial biomass burning exhibited episodes of persistent elevated activity, and a pivotal shift around 7000 years ago saw the boreal forest transition to an oak-pine barren ecosystem for about 2000 years before reverting. This mid-Holocene shift occurred during a period of more frequent burning and a sudden uptick in mean annual temperatures. Population size of Indigenous peoples mirrored wildfire fluctuations, decreasing with more frequent burning. Anticipated increases of fire activity with climate change are expected to echo transformations observed 7000 years ago, reducing boreal forest extent, and impacting land use.