Tolpyralate is a new Group 27 pyrazolone herbicide that inhibits the 4-hydroxyphenyl-pyruvate dioxygenase enzyme. In a study of the biologically effective dose of tolpyralate from 2015 to 2017 in Ontario, Canada, tolpyralate exhibited efficacy on a broader range of species when co-applied with atrazine; however, there is limited published information on the efficacy of tolpyralate and tolpyralate+atrazine relative to mesotrione and topramezone, applied POST with atrazine at label rates, for control of annual grass and broadleaf weeds. In this study, tolpyralate applied alone at 30 g ai ha−1 provided >90% control of common lambsquarters, velvetleaf, common ragweed, Powell amaranth/redroot pigweed, and green foxtail at 8 weeks after application (WAA). Addition of atrazine was required to achieve >90% control of wild mustard, ladysthumb, and barnyardgrass at 8 WAA. Tolpyralate+atrazine (30+1,000 g ai ha−1) and topramezone+atrazine (12.5+500 g ai ha−1) provided similar control at 8 WAA of the eight weed species in this study; however, tolpyralate+atrazine provided >90% control of green foxtail by 1 WAA. Tolpyralate+atrazine provided 18, 68, and 67 percentage points better control of common ragweed, green foxtail, and barnyardgrass, respectively, than mesotrione+atrazine (100+280 g ai ha−1) at 8 WAA. Overall, tolpyralate+atrazine applied POST provided equivalent or improved control of annual grass and broadleaf weeds compared with mesotrione+atrazine and topramezone+atrazine.