In this manuscript, we develop and analyze two high‐order schemes, CFD
and PQS
, for generalized variable coefficients fractional reaction–diffusion equations. The generalized fractional derivative is characterized by a weight function and a scale function. We approximate it using generalized Alikhanov formula (
) of order
, where
denotes the order of the generalized fractional derivative. Moreover, for spatial discretization, we use a compact operator in CFD
scheme and parametric quintic splines in PQS
scheme. The stability and convergence analysis of both schemes are demonstrated thoroughly using the discrete energy method in the
‐norm. It is shown that the convergence orders of the CFD
and PQS
schemes are
and
, respectively, where
and
represent the mesh spacing in the time direction and
is the mesh spacing in the space direction. In addition, numerical results are obtained for three test problems to validate the theory and demonstrate the efficiency and superiority of the proposed schemes.