Noble metal single-atom catalysts maximize metal utilization and offer opportunities to design heterogeneous catalysts at the molecular scale. Mesoporous covalent organic frameworks provide an ideal support to stabilize metal single atoms with specific ligand configuration similar to a homogeneous catalyst In this work, a high loading of single Pd atoms, 18.1 wt %, on mesoporous imine-linked covalent organic framework was synthesized, characterized, and evaluated for ethylene hydrogenation. X-ray photoelectron spectroscopy, X-ray absorption spectroscopy, and diffuse-reflectance infrared Fourier transform spectroscopy of adsorbed CO demonstrate that the Pd is atomically dispersed with a highly homogeneous local coordination. The Pd single atoms are active for hydrogenation of ethylene to ethane at room temperature. The study demonstrates that mesoporous COFs provide a large number of identical metal binding sites that are good candidates for immobilizing metal single atoms and their use in gas-phase catalytic applications.