The nonlinear and dynamic behavior of PEM fuel cells presents challenges for voltage regulation and motivates the development of advanced control strategies. This paper investigates advanced control methods for nonlinear processes in proton exchange membrane (PEM) fuel cell applications and presents a control structure for a 500 W Horizon H-500 PEM fuel cell. This fuel cell is represented by a nonlinear Hammerstein–Wiener model that was identified from experimental data. The study focuses on voltage regulation by reactant mass flow. The control structure uses a simplified approach with predefined constant stoichiometric ratios for reactant flow calculation instead of variable ratios based on the actual operating conditions of the fuel cell. Since PEM fuel cells are highly nonlinear systems, it is necessary to use control approaches that can handle these nonlinearities. Four advanced control approaches are discussed:  the linear quadratic regulator (LQR) with an integral term and gain scheduling (GS-LQR-I), sliding mode control, nonlinear model predictive control, and fuzzy logic control, each offering different trade-offs in terms of robustness, stability, and computational complexity. Among the considered approaches, GS-LQR-I was selected for implementation and further investigation. The LQR approach is based on a linear model of the controlled system. Therefore, local linear models needed to be derived from the nonlinear Hammerstein–Wiener model for gain-scheduled controller design. The resulting discrete-time closed-loop systems were analyzed using quadratic Lyapunov functions and the eigenvalues of the corresponding closed-loop system matrices. Numerical and graphical results for the selected GS-LQR-I method are presented. Control of PEM fuel cells is an important area of research and applied development because operating conditions strongly affect their efficiency, dynamic behavior, and lifetime. The proposed method demonstrated satisfactory control performance under the investigated operating conditions.