This study proposes a universal adaptive control algorithm for an unknown multi-input multi-output (MIMO) system using recursive least squares (RLS) and parameter self-tuning. The issue of adjusting the control and system parameters in response to changes in the platform was discussed. The development of a control algorithm that can consistently achieve reliable and robust control performance in various systems is important. This study aimed to develop a control algorithm that can track the reference value for any unknown MIMO system. For the controller design, an nth-order differential error dynamic model was designed, and an RLS with a scale factor was used to estimate the coefficients of the error dynamics. In the current scenario, the numbers of control inputs and error states in the error dynamics were assumed to be equal. It was designed such that the control input is derived based on the Lyapunov stability concept using the estimated coefficients. The scale factor in the RLS and injection term in the control input based on the sliding-mode approach were computed using a self-tuning methodology. The performance of the proposed universal adaptive control algorithm was evaluated using an actual DC motor and CarMaker (version 8.1.1) software tests under various scenarios.