Hierarchical mesoporous CuO@NiO nanoparticles were synthesized using metal−organic frameworks (MOFs) as the precursor. We investigated the physicochemical properties of the MOF-derived CuO@NiO (M-CuO@NiO) and its activity for the deoxygenation of fatty acids. High-resolution transmission electron microscopy (HRTEM) revealed that M-CuO@NiO possessed a homogeneous alloy configuration with well-dispersed CuO and NiO. X-ray photoelectron spectroscopy (XPS), thermogravimetric analysis (TGA), and temperature-programmed desorption (TPD) suggested that M-CuO@NiO retained the rich oxygen vacancies, excellent stability, and strong acidity, which are beneficial to the deoxygenation of fatty acids. The conversion of stearic acid (∼99.9%) and a selectivity of 94.4% to C8-C18 alkanes demonstrated the high activity of M-CuO@NiO, which is comparable to that of the noble catalyst Pt/C. In addition, a conversion of >99% for other fatty acids (lauric acid, palmitic acid, and oleic acid) and the selectivities of >90% for saturated fatty acids (lauric acid and palmitic acid) and 76.7% for oleic acid to C8-C18 alkanes indicate consistently high activity of M-CuO@NiO toward different fatty acids. Finally, we proposed the mechanistic pathways for the deoxygenation of stearic acid to C8-C18 alkanes. Overall, conclusions from this study support that M-CuO@NiO is a promising catalyst for the low-cost production of green diesel.