Maintaining stable tension is essential for ensuring the slitting quality of lithium battery separators. In particular, the precision of tension control in the unwinding system is critical to both product quality and process stability. This study proposes an optimized control strategy based on immune genetic algorithm-optimized active disturbance rejection control (IGA-ADRC) to address the tension regulation challenges in the unwinding system of lithium battery separator slitting machines. First, based on the operating mechanism of the unwinding system, a dynamic model was developed that incorporates time-varying parameters, nonlinear behavior, and strong coupling characteristics. Second, an active disturbance rejection controller was designed and optimized using an immune genetic algorithm, based on the tension dynamics of the unwinding system. Finally, the effectiveness of the proposed control strategy was validated through both simulations and experimental results. Simulation and experimental results demonstrate that the IGA-ADRC reduces tension deviation by 59.1% compared to proportional–integral–derivative control (from ±1.1 N to ±0.45 N) and by 25% compared to conventional ADRC (from ±0.6 N to ±0.45 N) while improving response speed and overshoot suppression. The proposed IGA-ADRC method achieves superior performance in terms of tension regulation accuracy, system robustness, and disturbance rejection capabilities.