This study investigated the influence of natural aging (NA) on the precipitation behavior of the main precipitate β″ and hardness evolution during the subsequent artificial aging (AA) process of the precipitation strengthened A357 aluminum alloy. The corresponding mechanisms were analyzed. The results demonstrate that natural aging has adverse influence on the precipitation process during artificial aging. The underlying mechanism is that small GP zones are formed during natural aging but cannot become nucleation sites for the β″ phase during artificial aging, which spontaneously consumes the supersaturated solute atoms in the Al matrix, increases the nucleation barrier of the β″ phase, and also consumes the vacancies produced after solid solution and quenching, thereby reducing the nucleation rate of the β″ phase during artificial aging, and leading to an un-expected increase in the size of the precipitated phase, thus reducing the peak aging hardness of the alloy. This effect becomes more pronounced with increasing natural aging time. Increasing the artificial aging temperature can improve the nucleation rate of the β″ phase during artificial aging, thereby to some extent reducing the unfavorable influence of natural aging on the artificial aging by reducing the sizes and increasing the amount of the β″ precipitates.