Field studies were conducted in 2008 and 2009 at three locations on the Texas Southern High Plains to evaluate grain sorghum response to saflufenacil alone or in combination with dimethenamid. Hybrids ‘Pioneer 85G01’ and ‘Dekalb 44-20’ were planted and saflufenacil at 0.5–0.70 kg ai ha−1 or saflufenacil + dimethenamid at 0.05 + 0.44 to 0.2 + 1.75 kg ai ha−1 was applied preemergence. Injury to sorghum increased with increasing rates at all locations. Saflufenacil + dimethenamid was less injurious than saflufenacil applied alone at similar rates. ‘Pioneer 85G01’ was more susceptible to herbicide injury than ‘Dekalb 44-20.’ Differences in soil texture and organic matter likely contributed to saflufenacil-induced injury across locations. Rainfall within 10 days after planting appeared to increase sorghum injury.