In this paper, we propose an upwind compact difference method with fourth-order spatial accuracy and second-order temporal accuracy for solving the streamfunction-velocity formulation of the two-dimensional unsteady incompressible Navier–Stokes equations. The streamfunction and its first-order partial derivatives (velocities) are treated as unknown variables. Three types of compact difference schemes are employed to discretize the first-order partial derivatives of the streamfunction. Specifically, these schemes include the fourth-order symmetric scheme, the fifth-order upwind scheme, and the sixth-order symmetric scheme derived by combining the two parts of the fifth-order upwind scheme. As a result, the fourth-order spatial discretization schemes are established for the Laplacian term, the biharmonic term, and the nonlinear convective term, along with the Crank–Nicolson scheme for the temporal discretization. The unconditional stability characteristic of the scheme for the linear model is proved by discrete von Neumann analysis. Moreover, six numerical experiments involving three test problems with the analytic solutions, and three flow problems including doubly periodic double shear layer, lid-driven cavity flow, and dipole-wall interaction are carried out to demonstrate the accuracy, robustness, and efficiency of the present method. The results indicate that the present method not only has good numerical performance but also exhibits quite efficiency.