Abstract In this study, we report the effect of water vapor on CO2 uptake using Mg-MOF-74 via adsorption breakthrough modeling and lab experiments. Carbon dioxide is the most influencing gas that significantly expedites global warming. Therefore, it is ultimately necessary to reduce the rapid increase of CO2 concentration in the atmosphere by means of Carbon Capture and Storage (CCS). CO2 separation by physical adsorption is an interesting technology to achieve CO2 capture with minimum energy penalties. Metal-organic framework (MOF) adsorbents forms a class of adsorbents with much higher specific surface areas than conventional porous materials such as activated carbons, and zeolites. However, most MOFs show notable hydro instability for CO2 separation from humid flue gas. Mg-MOF-74 is a superior adsorbent amongst other adsorbents owing to its high CO2 uptake at flue gas conditions. A model is developed using User-Defined-Function in an ANSYS Fluent program. Two and three-dimensional models are validated by comparing their results with experimental work carried out by the authors, at ambient temperature, and published experimental data for high temperature conditions. The effect of water vapor is studied at different temperatures and various relative humidity values for Mg-MOF-74. Results indicate that CO2 uptake has been significantly reduced with the existence of more than 5% water vapor when Mg-MOF-74 is used as an adsorbent.