This study presents a field-programmable gate array (FPGA)-based mechatronic design and real-time fuzzy control method with computational intelligence optimization for omni-Mecanum-wheeled autonomous vehicles. With the advantages of cuckoo search (CS), an evolutionary CS-based fuzzy system is proposed, called CS-fuzzy. The CS’s computational intelligence was employed to optimize the structure of fuzzy systems. The proposed CS-fuzzy computing scheme was then applied to design an optimal real-time control method for omni-Mecanum-wheeled autonomous vehicles with four wheels. Both vehicle model and CS-fuzzy optimization are considered to achieve intelligent tracking control of Mecanum mobile vehicles. The control parameters of the Mecanum fuzzy controller are online-adjusted to provide real-time capability. This methodology outperforms the traditional offline-tuned controllers without computational intelligences in terms of real-time control, performance, intelligent control and evolutionary optimization. The mechatronic design of the experimental CS-fuzzy based autonomous mobile vehicle was developed using FPGA realization. Some experimental results and comparative analysis are discussed to examine the effectiveness, performance, and merit of the proposed methods against other existing approaches.