The effects of Mn (peritectic system) and Zn (eutectic system) on the grain refinement of commercial pure Mg were investigated. Interdependence model and solute paradigm theory were applied to evaluate the grain nucleation and growth for these two alloy systems. Both Mn and Zn can refine the grain of pure Mg. Compared to Mg–Zn, the nucleant particles in Mg–Mn alloys are more potent, but the relatively activated number of nucleation sites is much fewer. Zn with relatively high value of growth restriction factor increases the initial rate of development of the constitutional supercooling (CS) zone at the earliest stage of grain growth, which plays a key role in determining the final grain size. Moreover, heavy segregation of Zn during solidification provides a driving-force to activate further nucleation in the CS zone, which may trigger some unknown native nucleation particles to sever as nuclei.