An atomic-scale approach was employed to simulate the formation of precipitates with different lattice misfits in the early stages of the aging of supersaturated aluminum alloys. The simulation results revealed that the increase in lattice misfits could significantly promote the nucleation rate of precipitates, which results in a larger number and smaller size of the precipitates. The morphologies of the precipitates also vary with the degree of a lattice misfit. Moreover, the higher the lattice misfit, the earlier the nucleation of the second phase occurs, which can substantially inhibit the movement of dislocations. The research on the lattice misfit of precipitation can provide theoretical guidance for the design of high-strength aluminum alloys.