Carbon dioxide conversion under realistic industrial conditions remains limited by the vulnerability of catalytic active sites toward moisture-induced deactivation. Here, we present a defect-programmed two-dimensional lanthanide–organic framework (NUC-210) that creates an adaptive catalytic microenvironment through the spatial integration of coordinatively unsaturated Dy3+ centers and multifunctional organic sites. Controlled activation of NUC-210 generates accessible Dy3+ Lewis acidic sites together with amino, pyridyl, and carboxylic acid functionalities, enabling cooperative activation of epoxides and CO2 within confined nanochannels. The activated framework (NUC-210a) exhibits outstanding catalytic efficiency for solvent-free CO2 cycloaddition with various epoxides, delivering turnover numbers up to 663 under mild conditions (100 ◦C, 1.0 MPa CO2). More importantly, NUC-210a preserves its catalytic function under simulated humid flue-gas conditions, maintaining 81.1% conversion after exposure to 95% relative humidity and fly ash while retaining structural integrity and recyclability. Density functional theory (DFT) calculations reveal a site-dependent catalytic hierarchy, where organic functional sites substantially reduce the energy barrier of CO2 insertion, whereas metalcentered Dy3+ sites primarily facilitate epoxide activation. These findings uncover an organic-site-amplified catalytic pathway that compensates for moisture-sensitive metal Lewis acidity and provides a new design principle for constructing robust heterogeneous catalysts. This work demonstrates that defect engineering can transform conventional MOF active sites into adaptive catalytic interfaces for practical carbon utilization from dilute and humid CO2 streams.
