Four field studies were conducted over a 3-yr period (2011 to 2013) to determine the tolerance of four soybean cultivars to pyroxasulfone (89 and 178 g ai ha−1), flumioxazin (71 and 142 g ai ha−1), and pyroxasulfone + flumioxazin (160 and 320 g ai ha−1) applied either preplant incorporated (PPI), PRE, or at the soybean cotyledon stage (COT). When pyroxasulfone + flumioxazin was applied at 160 and 320 g ai ha−1, at the cotyledon stage soybean yield was decreased by 9 and 14%, respectively. The only other treatment that decreased soybean yield was pyroxasulfone (178 g ai ha−1) applied PPI; yield was decreased by 6% despite minimal injury and dry biomass reductions observed during the season. Soybean tolerance to pyroxasulfone or flumioxazin applied alone was generally similar and injury was less than with pyroxasulfone + flumioxazin. Similarly, herbicides applied PPI and PRE were less injurious to soybean than the COT timing. Results suggest that soybean is tolerant to PPI and PRE applications of pyroxasulfone + flumioxazin but COT applications should be avoided.