We study the linear stability of plane Couette flow subject to an anisotropic slip boundary condition that models the slip effect of parallel microgrooves with a misalignment about the direction of the wall motion. This boundary condition has been reported to be able to destabilize channel flow far below the critical Reynolds number of the no-slip case. Unlike channel flow, the no-slip plane Couette flow is known to be linearly stable at arbitrary Reynolds numbers. Nevertheless, the results show that the slip can cause linear instability at finite Reynolds numbers also. The misalignment angle of the microgrooves that maximizes the destabilizing effect is nearly π/4, and the unstable modes are of small streamwise wavenumbers and relatively large spanwise wavenumbers. The flow is always more destabilized by two slippery walls compared to a single slippery wall. These observations are in qualitative agreement with the slippery channel flow with the same boundary condition, indicating that such an anisotropic superhydrophobic effect has a rather general destabilizing effect in shear flows regardless of the profile of the base flow. The absence of the Tollmien–Schlichting instability allows us to reveal the inverse relationship between the critical Reynolds number and the slip length as well as the misalignment in the small-parameter regime. The results suggest that arbitrary nonvanishing slip length and misalignment, with arbitrarily weak anisotropy, may suffice to destabilize plane Couette flow.