The vast tropical zone of the Congo Basin was historically an intact ecosystem shaped by climatic fluctuations and gradual presence of Hominins (modern humans and close relatives) dating back at least 730,000 years BP. Early hunter–gatherers of the Late Stone Age had minimal ecological impacts. From ~40,000 years BP, the Neolithic introduced slash-and-burn agriculture and iron smelting, pottery, and polished stone tools, leading to localized forest changes during the Iron Age. The Industrial Revolution accelerated transformation with colonial exploitation of timber, ivory, rubber, and other resources, combined with increased hunting and settlement that caused widespread deforestation, biodiversity loss, and human suffering through conflicts and diseases. Today, the Congo Basin remains a global biodiversity hotspot with over 15,000 vascular plant species, 450 mammal species, 1390 birds, diverse reptiles, amphibians, insects, and highly endemic freshwater fauna. Between 1990 and 2020, it lost roughly 8.5% of its forest cover due largely to smallholder agriculture, logging, mining, and urban expansion. These pressures have fragmented habitats, degraded water quality, and triggered Silent and Empty Forest and River Syndromes—where wildlife populations decline despite remaining forest cover. Key species, including forest elephants and gorillas, face critical threats from habitat destruction and poaching. Despite advances in genetic and remote sensing technologies coupled with regional conservation efforts, data gaps persist, and socio-political instability and lack of finance limits research and sustainable management. Balancing ecological preservation with human development needs remains urgent to protect the Congo Basin’s unparalleled biodiversity and its global climate role for future generations.