Field and greenhouse experiments were conducted to evaluate the efficacy and safening of metsulfuron applied with dicamba, 2,4-D, clopyralid, and fluroxypyr with and without nonionic surfactant. Greenhouse data showed that 2,4-D and dicamba, but not fluroxypyr, safened grain sorghum from metsulfuron injury. In the field study, grain sorghum injury from metsulfuron was decreased when tank mixed with 2,4-D or dicamba but not when tank mixed with clopyralid or fluroxypyr. Tank mixes of 2,4-D or dicamba with metsulfuron did not reduce ivyleaf morningglory or velvetleaf control. At 4 wk after treatment (WAT), ivyleaf morningglory was controlled 95, 84, 59, and 91%, and velvetleaf was controlled 88, 82, 78, and 95% when metsulfuron was tank mixed with 2,4-D, dicamba, clopyralid, and fluroxypyr, respectively. In a separate field study, differential grain sorghum hybrid responses to a tank mix of metsulfuron + 2,4-D was examined. In general, a tank mix of metsulfuron and 2,4-D caused visible injury to all hybrids at 1 and 2 WAT, but grain sorghum recovered and most hybrids appeared normal at the end of the growing season. Differential hybrid responses to metsulfuron + 2,4-D were observed at 1 and 2 WAT in 2000 and 4 WAT in 2001. The most susceptible hybrid was ‘Mycogen 1506’, and the least susceptible hybrids were ‘NK KS-310’ and ‘Pioneer 87G57’. This study demonstrates the potential for 2,4-D or dicamba to safen metsulfuron injury of sorghum without compromising weed control.