Nanotwinned metals exhibit superior mechanical properties due to unique dislocation–twin boundary interactions. In the present work, we elucidate the microscopic deformation mechanisms and their correlations with the macroscopic mechanical response of nanotwinned Al containing inclined twin boundaries under nanoindentation by means of molecular dynamics simulations. The effect of twin boundary orientation with respect to the indented surface on the nanoindentation is evaluated. Simulation results reveal that dislocation slip, dislocation–twin boundary interaction, and twin boundary migration operate in parallel in the plastic deformation of nanotwinned Al. The inclination angle of twin boundaries with respect to indented surface has a strong influence on the interaction between individual deformation modes, which in turn leads to the anisotropic indentation behavior of nanotwinned Al.