A potential human footprint on Western Central African rainforests before the Common Era has become the focus of an ongoing controversy. Between 3,000 y ago and 2,000 y ago, regional pollen sequences indicate a replacement of mature rainforests by a forest–savannah mosaic including pioneer trees. Although some studies suggested an anthropogenic influence on this forest fragmentation, current interpretations based on pollen data attribute the ‘‘rainforest crisis’’ to climate change toward a drier, more seasonal climate. A rigorous test of this hypothesis, however, requires climate proxies independent of vegetation changes. Here we resolve this controversy through a continuous 10,500-y record of both vegetation and hydrological changes from Lake Barombi in Southwest Cameroon based on changes in carbon and hydrogen isotope compositions of plant waxes. δ13C-inferred vegetation changes confirm a prominent and abrupt appearance of C4 plants in the Lake Barombi catchment, at 2,600 calendar years before AD 1950 (cal y BP), followed by an equally sudden return to rainforest vegetation at 2,020 cal y BP. δD values from the same plant wax compounds, however, show no simultaneous hydrological change. Based on the combination of these data with a comprehensive regional archaeological database we provide evidence that humans triggered the rainforest fragmentation 2,600 y ago. Our findings suggest that technological developments, including agricultural practices and iron metallurgy, possibly related to the large-scale Bantu expansion, significantly impacted the ecosystems before the Common Era.