Power systems have recently faced significant challenges due to the increased penetration of renewable energy sources (RES) such as frequency deviation due to fluctuations, unpredictable nature, and uncertainty of this RES. In this paper, a cascaded controller called (1+PD)-PID is proposed to reduce the influence of RES uncertainties on the system and to maintain the system’s reliability during fluctuations. The proposed controller is a combination of (1+PD) and PID controllers in order. The output signal of the (1+PD) controller along with the frequency deviation and the power difference between adjacent areas are used as inputs to the PID controller to create the load reference signal. The parameters of the suggested controller are optimally tuned using the African Vulture Optimization Algorithm (AVOA) to ensure the best performance of the controller. A two-area interconnected system with non-reheat thermal power units combined with RES such as solar and wind energy is modeled using MATLAB/Simulink to evaluate the system response. The controller effectiveness is verified by subjecting the studied system to various types of fluctuations such as step load disturbance, variable load perturbation and RES penetration. The obtained simulation results prove that the proposed (1+PD)-PID controller in integration with AVOA offers a significant improvement in the system performance specifications. Moreover, the proposed AVOA-based (1+PD)-PID controller has proven its superiority over other comparable controllers having the least fitness function of 6.01 × 10−5.