Tolpyralate is a new 4-hydroxyphenyl-pyruvate dioxygenase (HPPD)-inhibiting herbicide for POST weed management in corn; however, there is limited information regarding its efficacy. Six field studies were conducted in Ontario, Canada, over 3 yr (2015 to 2017) to determine the biologically effective dose of tolpyralate for the control of eight annual weed species. Tolpyralate was applied POST at six doses from 3.75 to 120 g ai ha−1 and tank mixed at a 1:33.3 ratio with atrazine at six doses from 125 to 4,000 g ha−1. Regression analysis was performed to determine the effective dose (ED) of tolpyralate, and tolpyralate+atrazine, required to achieve 50%, 80%, or 90% control of eight weed species at 1, 2, 4, and 8 wk after application (WAA). The ED of tolpyralate for 90% control (ED90) of velvetleaf, common lambsquarters, common ragweed, redroot pigweed or Powell amaranth, and green foxtail at 8 WAA was ≤15.5 g ha−1; however, tolpyralate alone did not provide 90% control of wild mustard, barnyardgrass, or ladysthumb at 8 WAA at any dose evaluated in this study. In contrast, the ED90 for all species in this study with tolpyralate+atrazine was ≤13.1+436 g ha−1, indicating that tolpyralate+atrazine can be highly efficacious at low field doses.