We perform a theoretical and experimental investigation of the magnetic properties of a series of Mn-substituted non-stoichiometric cobalt ferrite nanopowders. We propose a theoretical approach based on the Stoner–Wohlfarth model of coherent rotation of single-domains, considering mean-field interactions between the nanograins. In particular, we provide a detailed description of the magnetic anisotropy behavior, considering tetragonal distortions of the cubic spinel structure of the system. Our model shows that the effects of the tetragonal distortion of the cubic structure may be modeled by a superposition of uniaxial and cubic magnetocrystalline anisotropies. We obtain the uniaxial and cubic anisotropy constants and the mean-field parameters by fitting numerically the experimental magnetic hysteresis curves. Thus, the agreement between theory and experiment provides support to confirm the validity of our theoretical approach, in addition our results corroborate experimental works found in the literature reporting that cobalt ferrites present tetragonal distortion of the well-known cubic spinel structure