The widespread evolution of resistance in rigid ryegrass populations to the highly effective, in-crop, selective herbicides used within southern Australian grain-crop production systems has severely diminished the available herbicide resource. A new PRE grass-selective herbicide, pyroxasulfone, may offer Australian grain producers a new option for rigid ryegrass control in wheat crops. The efficacy and level of selectivity of rigid ryegrass control with pyroxasulfone was investigated for a range of annual crop species in potted-plant, dose–response studies. In comparison with other currently available PRE herbicides, pyroxasulfone provided effective control of both resistant and susceptible rigid ryegrass populations. Additionally, control of these populations was achieved at rates that had little or no effect on the growth and survival of wheat. This crop was also the most tolerant of cereal species, with triticale, barley, and oat being more injured at higher pyroxasulfone rates than wheat was. In general though, pulse-crop species were found to be more tolerant of high pyroxasulfone rates than cereal-crop species. There were subtle effects of soil type on the efficacy of pyroxasulfone, where higher rates were required to achieve effective control on soils with higher clay or organic matter contents. The ability of pyroxasulfone to selectively control resistant and susceptible rigid ryegrass populations as identified in these studies clearly indicate the potential for widespread use and success of this herbicide in Australian cropping systems.