The main aim of this study was to develop a new process for nickel recovery from low-grade nickel laterite and to investigate its usability as an alternative and low-cost process. The process consists of two main steps: first, the treatment of laterite by reagent-assisted mechanochemical conversion (R-MC); second, recovery of nickel from treated laterite with (U-AL) and without (AL) ultrasound-assisted leaching. R-MC processes were carried out using Na2SO4 and Na2CO3 as reagents. The effect of reagents was investigated by evaluating the leaching selectivity of nickel over iron. Response Surface Methodology (RSM) was used to improve the performance of the processes. Nickel recoveries were achieved over 90% for both processes. The dissolution of nickel and iron from R-MC treated laterite was controlled by a combination of chemical and diffusion reactions for both leaching processes. Moreover, it was also observed for both leaching processes that dissolution activation energies of nickel and iron from R-MC treated laterite, were markedly reduced compared to raw laterite. According to results, the synergistic effect of both ultrasonic power and mechanochemistry on the leaching process contributes positively to the completion of the leaching in a shorter time by accelerating the reaction and facilitating the mass transfer.