In order to improve the pressure tracking response of an artificial ventilator system, a novel proportional integral derivative (PID) controller is designed in the present work by utilizing an optimal rule-based fuzzy inference system (FIS) with a reshaped class-topper optimization algorithm (RCTO), which is named as (Fuzzy-PID). Firstly, a patient-hose blower-driven artificial ventilator model is considered, and the transfer function model is established. The ventilator is assumed to operate in pressure control mode. Then, a fuzzy-PID control structure is formulated such that the error and change in error between the desired airway pressure and actual airway pressure of the ventilator are set as inputs to the FIS. The gains of the PID controller (proportional gain, derivative gain, and integral gain) are set as outputs of the FIS. A reshaped class topper optimization algorithm (RCTO) is developed to optimize rules of the FIS to establish optimal coordination among the input and output variables of the FIS. Finally, the optimized Fuzzy-PID controller is examined for the ventilator under different scenarios such as parametric uncertainties, external disturbances, sensor noise, and a time-varying breathing pattern. In addition, the stability analysis of the system is carried out using the Nyquist stability method, and the sensitivity of the optimal Fuzzy-PID is examined for different blower parameters. The simulation results showed satisfactory results in terms of peak time, overshoot, and settling time for all cases, which were also compared with existing results. It is observed in the simulation results that the overshoot in the pressure profile is improved by 16% with the proposed optimal rule based fuzzy-PID as compared with randomly selected rules for the system. Settling time and peak time are also improved 60–80% compared to the existing method. The control signal generated by the proposed controller is also improved in magnitude by 80–90% compared to the existing method. With a lower magnitude, the control signal can also avoid actuator saturation problems.