Field experiments were conducted at Belleville, Colby, Hays, Hesston, Garden City, and Manhattan, KS, to determine grain sorghum response to POST application of mesotrione at three application timings. Mesotrione was applied at 52, 105, 157, and 210 g ai/ha in combination with 280 g ai/ha atrazine to grain sorghum at heights of 5 to 8, 15 to 20, and 30 cm, which correspond to early POST (EPOST), mid-POST (MPOST), and late POST (LPOST), respectively. All mesotrione rates caused injury at all application timings. Overall, grain sorghum injury from mesotrione was greatest at 1 wk after treatment (WAT); plants partially recovered from injury by 4 WAT. Mesotrione applied EPOST injured grain sorghum more than when applied at MPOST and LPOST timings. The EPOST application injured grain sorghum 19 to 88%, whereas injury from MPOST and LPOST application was 1 to 66% and 0 to 69%, respectively, depending on rate. Mesotrione injury was least at Belleville and most at the Hesston and Garden City (irrigated) sites regardless of growth stage. Correlation coefficient analyses indicated that observed mesotrione injury symptoms were not well correlated with grain sorghum yield; thus, mesotrione injury to grain sorghum did not influence grain yield. However, initial grain sorghum injury was severe, and this will likely be a major concern to producers.