CDREG develops the major new Earth system science research hypothesis that tectonic-related variations in Earth’s atmospheric CO2 concentration ([CO2]a) drive negative ecological feedbacks on terrestrial silicate weathering rates that stabilise further [CO2]a change and regulate climate. This paradigm-changing hypothesis integrates ecological and abiotic controls on silicate weathering to understand how terrestrial ecosystems have shaped past Earth system dynamics. The proposed ecological feedbacks are mechanistically linked to the extent and activities of forested ecosystems and their symbiotic fungal partners as the primary engines of biological weathering.CDREG’s core hypothesis establishes an exciting cross-disciplinary Research Programme that offers novel opportunities for major breakthroughs implemented through four linked hypothesis-driven work packages (WPs) employing experimental, geochemical and numerical modelling approaches. WP1 quantitatively characterises [CO2]a-driven tree/grass-fungal mineral weathering by coupling metabolic profiling with advanced nanometre scale surface metrological techniques for investigating hyphal-mineral interactions. WP2 quantifies the role [CO2]a-drought interactions on savanna tree mortality and C4 grass survivorship, plus symbiotic fungal-driven mineral weathering. WP3 exploits the past 8 Ma of marine sediment archives to investigate the links between forest to savanna transition, terrestrial weathering, fire, and climate in Africa. WP4 integrates findings from WP1-3 into a new Earth system modelling framework to rigorously investigate the biogeochemical feedbacks of [CO2]a-regulated ecological weathering on [CO2]a via marine carbonate deposition and organic C burial.The ultimate goal is to provide a new synthesis in which the role of [CO2]a in regulating the ecological weathering engine across scales from root-associated microorganisms to terrestrial ecosystems is mechanistically understood and assessed.