This study presents the first regional-scale assessment of estuarine CO₂ evasion along the US East Coast (25–45° N). The focus is on 42 tidal estuaries, which together drain a catchment of 697 000 km² or 76 % of the total area within this latitudinal band. The approach is based on the Carbon–Generic Estuary Model (C-GEM) that allows the simulation of hydrodynamics, transport, and biogeochemistry for a wide range of estuarine systems using readily available geometric parameters and global databases of seasonal climatic, hydraulic, and riverine biogeochemical information. Our simulations, performed using conditions representative of the year 2000, suggest that, together, US East Coast estuaries emit 1.9 Tg C yr⁻¹ in the form of CO₂, which corresponds to about 40 % of the carbon inputs from rivers, marshes, and mangroves. Carbon removal within estuaries results from a combination of physical (outgassing of supersaturated riverine waters) and biogeochemical processes (net heterotrophy and nitrification). The CO₂ evasion and its underlying drivers show important variations across individual systems, but reveal a clear latitudinal pattern characterized by a decrease in the relative importance of physical over biogeochemical processes along a north–south gradient. Finally, the results reveal that the ratio of estuarine surface area to the river discharge, S∕Q (which has a scale of per meter discharged water per year), could be used as a predictor of the estuarine carbon processing in future regional- and global-scale assessments.