Atrazine offers growers a reliable option to control a broad spectrum of weeds in grain sorghum production systems when applied PRE or POST. However, because of the extensive use of atrazine in grain sorghum and corn, it has been found in groundwater in the United States. Given this issue, field experiments were conducted in 2017 and 2018 in Fayetteville and Marianna, Arkansas, to explore the tolerance of grain sorghum to applications of assorted photosystem II (PSII)-inhibiting herbicides in combination with S-metolachlor (PRE and POST) or mesotrione (POST only) as atrazine replacements. All experiments were designed as a factorial, randomized complete block; the two factors were (1) PSII herbicide and (2) the herbicide added to create the mixture. The PSII herbicides were prometryn, ametryn, simazine, fluometuron, metribuzin, linuron, diuron, atrazine, and propazine. The second factor consisted of either no additional herbicide, S-metolachlor, or mesotrione; however, mesotrione was excluded in the PRE experiments. Crop injury estimates, height, and yield data were collected or calculated in both studies. In the PRE study, injury was less than 10% for all treatments except those containing simazine, which caused 11% injury 28 d after application (DAA). Averaged over PSII herbicide, S-metolachlor–containing treatments caused 7% injury at 14 and 28 DAA. Grain sorghum in atrazine-containing treatments yielded 97% of the nontreated. Grain sorghum receiving other herbicide treatments had significant yield loss due to crop injury, compared with atrazine-containing treatments. In the POST study, ametryn- and prometryn-containing treatments were more injurious than all other treatments 14 DAA. Grain sorghum yield in all POST treatments was comparable to atrazine, except prometryn plus mesotrione, which was 65% of the nontreated. More herbicides should be evaluated to find a comparable fit to atrazine when applied PRE in grain sorghum. However, when applied POST, diuron, fluometuron, linuron, metribuzin, propazine, and simazine have some potential to replace atrazine in terms of crop tolerance and should be further tested as part of a weed control program across a greater range of environments.