Homogenously dispersed, ultrafine Ni nanoparticles (Ni NPs) have been grown in a mesoporous carbon (MC) matrix (MC-Niinsitu) and efficiently catalyze low-temperature hydrogen desorption from Mg(BH4)2. The onset desorption temperature (Tonset) of this MC-Niinsitu-Mg(BH4)2 system is 44 °C compared to 275 °C (Tonset) for pure Mg(BH4)2. This is the lowest value reported for hydrogen desorption from this metal hydride. The activation energy (Ea) of MC-Niinsitu-Mg(BH4)2 was determined to be 21.3 kJ/mol which is less than half the value of 45.9 kJ/mol for pure Mg(BH4)2. We ascribe this reduction to the synergistic effects of nanoconfinement and the homogeneously dispersed, ultrafine Ni NPs active sites in the mesoporous carbon.