In 2015, winter wheat growers in Virginia reported commercial failures of thifensulfuron to control mouse-ear cress. This was the first reported case of field-evolved acetolactate synthase (ALS) resistance in mouse-ear cress, so research was conducted to evaluate alternative herbicide options as well as to document potential yield loss in winter wheat from mouse-ear cress. Efficacy studies were conducted at three site-years in 2015 to 2016 and 2016 to 2017 as well as a POST greenhouse trial. In the PRE study, flumioxazin, pyroxasulfone, saflufenacil, and metribuzin resulted in more than 80% mouse-ear cress control 15 wk after planting across all sites with no observable wheat injury. No differences were observed in wheat yield in two of three sites in the PRE herbicide study; yield differences were attributed to common chickweed and not to mouse-ear cress. In the POST herbicide study, 2,4-D, dicamba, and metribuzin resulted in greater than 75% control in the field and greenhouse. Metribuzin, dicamba, and pyroxsulam resulted in crop injury 3 wk after treatment at some sites, but injury was transient. Yield from all POST treatments was similar to the nontreated plots. No yield loss was observed by mouse-ear cress densities greater than 300 plants m–2, indicating that mouse-ear cress is not very competitive with winter wheat. Growers should make herbicide decisions based on other weeds in the field and can incorporate the aforementioned herbicides for mouse-ear cress control.