The effect of Sc and Zr on the fatigue property of Al-6.2Mg-0.4Mn alloy was investigated by control experiment; the fatigue lives of Al-6.2Mg-0.4Mn alloy with and without Sc and Zr at different loading stress amplitudes were measured. The relationships between their fatigue properties and microstructures were studied by means of optical microscope, scanning electronic microscope and transmission electron microscope. The addition of Sc and Zr improved the fatigue lives and fatigue strength of Al-6.2Mg-0.4Mn alloy. It is difficult for crack to initiate and propagate in the Al-6.2Mg-0.4Mn-Sc-Zr alloy. The fine and pancake-like grains of this alloy lead to the increase of fatigue life and fatigue strength. The high densities of dislocation and grain boundary in the Al-6.2Mg-0.4Mn-Sc-Zr alloy can prevent microcrack from propagating effectively. Additionally the dispersion precipitation of Al3Sc and Al3(Sc1-xZrx) particles enhance the toughness of Al-6.2Mg-0.4Mn-Sc-Zr alloy.