The causes of the variations in CO2 of the past million years remain poorly understood. Imbalances between the input of elements from rock weathering and their removal from the atmosphere-ocean-biosphere system to the lithosphere likely contributed to reconstructed changes. We employ the Bern3D Earth system model of intermediate complexity to investigate carbon-climate responses to step-changes in the weathering input of phosphorus, alkalinity, carbon, and carbon isotope ratio (δ13C) in simulations extending up to 600,000 years. CO2 and climate approach a new equilibrium within a few ten thousand years, whereas the equilibration lasts several hundred thousand years for δ13C. These timescales represent a challenge for the initialization of sediment-enabled models and unintended drifts may be larger than forced signals in simulations of the last glacial-interglacial cycle. Changes in dissolved CO2 change isotopic fractionation during marine photosynthesis and δ13C of organic matter. This mechanism and changes in the organic matter export cause distinct spatio-temporal perturbations in δ13C of dissolved inorganic carbon. A cost-efficient emulator is built with the Bern3D responses and applied in contrasting literature-based weathering histories for the past 800,000 years. Differences between scenarios for carbonate rock weathering reach around a third of the glacial-interglacial CO2 amplitude, 0.05 ‰ for δ13C, and exceed reconstructed variations in marine carbonate ion. Plausible input from the decomposition of organic matter on shelves causes variations of up to 10 ppm in CO2 , 4 mmol m−3 in CO2−3, and 0.09‰ in δ13C. Our results demonstrate that weathering-burial imbalances are important for past climate variations.