The two-volume set LNAI 13612 and 13613 constitutes the proceedings of the 21st Mexican International Conference on Artificial Intelligence, MICAI 2022, held in Monterrey, Mexico, in October 2022. The total of 63 papers presented in these two volumes was carefully reviewed and selected from 137 submissions. The first volume, Advances in Computational Intelligence, contains 34 papers structured into three sections: Machine and Deep Learning Image Processing and Pattern Recognition Evolutionary and Metaheuristic Algorithms The second volume contains 29 papers structured into two sections: Natural Language Processing Intelligent Applications and Robotics