This study presents a novel automatic tuning method for cascade control systems in which both primary and secondary controllers are tuned simultaneously using a single closed-loop step test. The proposed technique identifies the required process information with the help of B-spline series representation for the step responses. The two proportional–integral–derivative (PID) controllers are then tuned using an internal model control (IMC) approach. Considering the rationale of cascade control, the secondary controller is designed for faster disturbance attenuation. Without requiring an additional experiment, the primary controller is designed based on an identified process model that accurately accounts for inner loop dynamics. Finally, this study includes robustness considerations in the controller tuning process, and develops explicit guidelines for the selection of the IMC tuning parameters, completing the automatic tuning procedure for cascade control systems. The proposed method is robust to measurement noise because of the filtering property of the B-splines, and can provide superior control performance for both set-point tracking and disturbance rejection. Simulation examples demonstrate the effectiveness of the proposed automatic tuning method.