We propose and analyze a meshless method of lines by considering some hybrid radial kernels. These hybrid kernels are constructed by linearly combining infinite smooth radial functions to piecewise smooth radial functions; which are then used for spatial approximation on trial spaces spanned by translates of positive definite radial functions. After spatial approximation, a high-order ODE solver is invoked for efficient and stable time-integration of the resultant semi-discrete system of ordinary differential equations (ODEs). Unlike the mesh-based method of lines, the proposed method works for arbitrary scattered data points and is equally effective for problems over non-rectangular domains. The proposed method is tested on one-, two- and three-dimensional reaction–diffusion Fisher equation for its numerical stability, accuracy, and efficiency against the contemporary meshless and mesh-based methods. The economical computational cost, improved accuracy, eigenvalues stability, and well-conditioning of system matrices are observed against RBF collocation and RBF-PS methods.