This work employs newly shifted Lucas polynomials to approximate solutions to the time-fractional Fitzhugh–Nagumo differential equation (TFFNDE) relevant to neuroscience. Novel essential formulae for the shifted Lucas polynomials are crucial for developing our suggested numerical approach. The analytic and inversion formulas are introduced, and after that, new formulas that express these polynomials’ integer and fractional derivatives are derived to facilitate the construction of integer and fractional operational matrices for the derivatives. Employing these operational matrices with the typical collocation method converts the TFFNDE into a system of algebraic equations that can be addressed with standard numerical solvers. The convergence analysis of the shifted Lucas expansion is carefully investigated. Certain inequalities involving the golden ratio are established in this context. The suggested numerical method is evaluated using several numerical examples to verify its applicability and efficiency.