Grain growth of nanostructured Al6061 produced by cryorolling and aging process was investigated during isothermal heat treatment in 100–500 °C temperature range. Transmission electron microscopy (TEM) observations demonstrate that after cryorolling and aging at 130 °C for 30 h, the microstructure contains 61 nm grains with dispersed 50–150 nm precipitates and 0.248% lattice strain. In addition, an increase in tensile strength up to 362 MPa because of formation of fine strengthening precipitation and nano-sized grains was observed. Thermal stability investigation within 100–500 °C temperature range showed release of lattice strain, dissolution of precipitates and grain growth. According to the X-ray diffraction (XRD) analysis, Mg2Si precipitates disappeared after annealing at temperatures higher than 300 °C. According to the results, due to the limited grain growth up to 200 °C, there would be little decrease in mechanical properties, but within 300–500 °C range, the grain growth, dissolution of strengthening precipitates and decrease in mechanical properties are remarkable. The activation energies for grain growth were calculated to be 203.3 kJ/mol for annealing at 100–200 °C and 166.34 kJ/mol for annealing at 300–500 °C. The effect of precipitation dissolution on Al lattice parameter, displacement of Al6061 (111) XRD peak and Portevin–LeChatelier (PLC) effect on stress–strain curves is also discussed.