Anomalous diffusion of particles has been described by the time-fractional reaction–diffusion equation. A hybrid formulation of numerical technique is proposed to solve the time-fractional-order reaction–diffusion (FRD) equation numerically. The technique comprises the semi-discretization of the time variable using an L1 finite-difference scheme and space discretization using the quintic Hermite spline collocation method. The hybrid technique reduces the problem to an iterative scheme of an algebraic system of equations. The stability analysis of the proposed numerical scheme and the optimal error bounds for the approximate solution are also studied. A comparative study of the obtained results and an error analysis of approximation show the efficiency, accuracy, and effectiveness of the technique.