Porous octahedral copper-based metal organic framework MOF-199 anchored with Ru, RuMo, RuP, and RuMoP nanoparticles (NPs) was fabricated by a simple liquid impregnation method and applied as a high-performance catalyst for the hydrolysis of ammonia borane (AB) at room temperature. Comparison of the catalytic activities of Ru@MOF-199, RuMo@MOF-199, RuP@MOF-199, and commercial Ru/C shows that RuMoP@MOF-199 owns a very high turnover frequency of 735.6 mol H2 min−1 (mol Ru)−1 and a low activation energy of 46.9 kJ/mol. Loading RuMoP NPs onto MOF-199 owing to synergistic effects, functional, size, and support effects kinetically facilitates the oxidative cleavage of attacked H-OH and elevate the catalytic performance. Moreover, this catalyst shows satisfied durability after five cycles for the hydrolytic dehydrogenation of AB. The novel structural features and efficient performance would provide an essential reference for the utilization of high-performance catalyst development.