The influence of crystal orientation (including [100], [110], and [111]) and diameter (ranging from 2 to 10 nm) on the tensile deformation behavior and mechanical properties of single-crystal spinel (MgAl2O4) nanowires is investigated using molecular dynamics simulations. Varied deformation characteristics and fracture modes are revealed when the tensile loading is applied in the differently oriented nanowires. Mechanical properties including elastic modulus and ultimate tensile strength of spinel nanowires are distinctly dependent on size in each crystal orientation. This study advances the understanding of spinel nanomechanics which can help the development of high-strength spinel materials and their potential nanodevice applications.