A comprehensive two‐dimensional mathematical model based on surface renewal theory has been developed to analyze the CO2 absorption into piperazine (PZ)‐activated aqueous N‐methyldiethanolamine (MDEA) solvent by taking into account the structured packed bed column hydraulics, mass transfer resistances, and chemical reactions. The modeling results have been validated with the experimental data reported in the literature, and they have been found to be in good agreement with the experimental results. The effects of amine concentration, liquid temperature, initial CO2 partial pressure, liquid flow rate, and CO2 loading on the mass transfer performance have been evaluated in terms of overall mass transfer coefficient (KGav). The overall mass transfer coefficient and absorption flux of CO2 into aqueous MDEA+PZ blended solution have been calculated over the CO2 partial pressure range of 4–16 kPa, temperature range of 298–333 K, and solvent concentration of 1–3 M. To evaluate the performance of different solvents on separation process, some common industrial chemical absorbents including monoethanolamine (MEA), diethanolamine (DEA), triethylamine (TEA), MDEA and PZ were compared with a MDEA+PZ blended solution. The results indicate that CO2 absorption reaction with PZ is faster than that with MDEA, but also adding small amounts of PZ as a promoter to MDEA solvents improves significantly the absorption rate. The results show that CO2 absorption reaction with the MDEA+PZ blended solution is faster than that with TEA and MDEA, also comparable with DEA, but slower than those with MEA and PZ. The modeling results illustrate that the KGav enhances with increasing the solvent concentration, liquid temperature, and liquid flow rate, but reduces with increasing the CO2 loading and initial CO2 partial pressure. In addition, the reaction kinetics in terms of enhancement factor was found to decrease as the CO2 loading enhances and increase as the operating temperature rises.