The advancement of efficient carbon capture technology is vital for the transition to a net-zero carbon future. Critical developments in ultrasonic irradiation can be used to enhance the conventional CO2 absorption process. For example, sonophysical effects such as acoustic streaming, acoustic cavitation, acoustic fountain and atomization induced by the propagation of high-frequency ultrasonic waves in a liquid medium can enhance the mixing and create a larger interfacial area for gas�liquid mass transfer. In this study, the performance of a continuous ultrasonic-assisted CO2 absorption process using MDEA was investigated. The design of experiment (DOE) was used to study the effect of the gas flowrate, liquid flowrate and ultrasonic power on CO2 absorption performance. Based on the findings, ultrasonic power was the most significant parameter affecting the CO2 outlet concentration, liquid-to-gas ratio (L/G) and mass transfer coefficient (KGa), which confirmed that ultrasonic irradiation has a significant impact on the intensification of the CO2 absorption process. The optimum condition to achieve the target CO2 absorption performance was numerically determined and validated with experimental tests. The results from the verification runs were in good agreement with the predicted values, and the average error was less than 10. © 2023 by the authors.