Microalloying addition plays a significant role in controlling the characteristics of precipitates in Al alloys. This study investigates the effects of Ag and Sc microalloying addition on the thermal stability of Al–Zn–Mg–Cu alloys, via differential scanning calorimetry, transmission electron microscopy, and atom-probe tomography. The results demonstrate that Ag and Sc additions increase the number density of η-MgZn2 type nano-precipitates (formed during heat treatment) by forming direct (Mg–Ag phase, prototype of precipitate) or indirect precursors (Al2Sc phase, constituent of precipitate) for the precipitate. In addition, the Ag and Sc elements can effectively prevent the coarsening of η precipitates and facilitate the high-density distribution of fine η precipitates, during the over-aging period, improving the thermal stability of the Al–Zn–Mg–Cu alloys. The thermal stability is particularly improved by Ag addition because Ag atoms directly prevent the coarsening of η precipitates by hindering Zn diffusion into the precipitate. On the contrary, Sc addition indirectly prevents the coarsening of η precipitates by depleting the solute species from the Al matrix, enabling abundant precipitates limited growth. Thus Ag addition improves precipitation strengthening by preventing the coarsening of precipitates during over-aging.