Saflufenacil (Sharpen) is a commonly used preplant herbicide for the control of broadleaf weeds in corn (Zea mays) and soybean (Glycine max). Water hardness can influence the efficacy of some herbicides. Field experiments were conducted in Lafayette, IN, in 2012 to determine the influence of water hardness and co‐applied herbicides on the efficacy of saflufenacil. Saflufenacil application with any herbicide provided 12 to 33% higher control of common lambsquarters (Chenopodium album L.) as compared to saflufenacil alone, and saflufenacil with atrazine (Aatrex), clethodim (Select Max), cloransulam‐methyl (FirstRate), dicamba (Clarity), isoxaflutole (Balance Pro), mesotrione (Callisto), metribuzin (Metribuzin 75), paraquat (Gramoxone Inteon), or 2,4‐D (Weedar 64) provided at least 90% control of common lambsquarters at 21 days after treatment (DAT). Tank‐mix of saflufenacil with other herbicides controlled giant ragweed by at least 85%. Regardless of rating intervals, saflufenacil combinations with glufosinate (Ignite) or glyphosate (Roundup Powermax) provided 96% or 100% control of giant foxtail, respectively. Conversely, saflufenacil application with imazaquin and imazethapyr only provided 29 to 65% control of giant foxtail. When saflufenacil was applied alone at 0.36 oz ai/acre and without diammonium sulfate, common lambsquarters control was reduced by water sources having hardness of 310 ppm or 620 ppm as compared to deionized water without diammonium sulfate. When diammonium sulfate was included at 0.17 lb/gal, no differences were observed between water hardness levels. There was no influence of water hardness on saflufenacil efficacy of giant ragweed.