Bio-efficacy and phytotoxicity of pre-emergence tank mix application of atrazine + pendimethalin, pendimethalin + imazethapyr, ready mix application of pendimethalin+ imazethapyr (Velore), imazethpyr + imazamox (Odessey), penoxsulam, and post-emergence application of penoxsulam, atrazine, imazethapyr and imazethpyr + imazamox along with standard pre-emergence herbicide atrazine were evaluated at ICAR-Indian Institute of Millet Research, Hyderabad during rainy season of 2014. The field was dominated with broad-leaved weeds (65.8%) followed by grasses (26.3%) and sedges (7.9%). Infestation of weeds throughout the cropping season caused 37% reduction in grain yield. Post-emergence (15 DAS) application of imazethapyr and velore herbicides was highly phytotoxic and caused complete mortality of both sorghum plants and weeds at 2 weeks after herbicide application. Tank mix application of atrazine + pendimethalin (500 + 750 g/ha) as pre-emergence was safe and most effective in sorghum. Atrazine as post-emergence was less effective than its pre-emergence application. New herbicide molecules viz., penoxsulam, velore and odessey, though effectively controlled the weeds but reduced the grain yield due to reduction in number of grains/panicle.