Field experiments were conducted at Lacombe and Ellerslie, Alberta, Canada, to study the interaction of tillage with glyphosate and sethoxydim on quackgrass shoot and rhizome biomass, rhizome bud viability, and crop yield. Glyphosate was most effective in the conventional tillage regime, whereas sethoxydim was effective only in conventional tillage. Tillage reduced viable rhizome buds more than shoot or rhizome biomass. The large tillage effect on quackgrass control with either herbicide would likely be diminished in zero tillage systems that employ preseeding burn-off or preharvest application of glyphosate. Under zero and conventional tillage, glyphosate at 220 g ha−1 often was as effective as glyphosate at 880 g ha−1.A split application of glyphosate at 220 g ha−1 in the fall and spring was as effective as a single 880 g ha−1 treatment in conventional tillage, and sometimes more effective than 880 g ha−1 in zero tillage. Glyphosate followed by sethoxydim was usually no better than glyphosate alone. Short-term split applications of sethoxydim offered no consistent advantage over single applications.