The dynamic evolution of particles in limestone with a wide size distribution is significant for in-furnace desulfurization in circulating fluidized beds (CFB). In this study, air/SO2 mixtures were selected to simulate the flue gas combustion atmosphere, and the evolution on particle size of limestone with a wide size distribution was investigated using a self-built fluidized bed, with a focus on the evolution mechanism. The results show that the change in the cumulative particle size distribution (PSD) of limestone with a wide size distribution exhibited three stages as a function of reaction time. The cumulative PSD decreased continuously and reached 79.3% after 20 min during the first stage. The cumulative PSD was unchanged from 30 to 120 min in the second stage. The cumulative PSD increased from 81.9% to 88.3% in the range of 120–240 min during the third stage. The effects of attrition, heat stress, calcination, and sulfation on the changes in particle size were quantified and correlated with time. A novel method is proposed to predict the evolution mechanism of limestone with a wide size distribution. Calcination dominated in the time range of 0–60 min, and the predominant effect transformed from calcination to attrition at 240 min. However, the contribution of calcination was not negligible. The evolution of limestone with a wide size distribution can be promoted by the interactions of different effects.