Effective POST herbicides and herbicide mixtures are key components of integrated weed management in corn; however, herbicides vary in their efficacy based on application timing. Six field experiments were conducted over 2 yr (2017–2018) in southwestern Ontario, Canada, to determine the effects of herbicide application timing and rate on the efficacy of tolpyralate, a new 4-hydroxyphenyl pyruvate dioxygenase inhibitor. Tolpyralate at 15, 30, or 40 g ai ha−1 in combination with atrazine at 500 or 1,000 g ai ha−1 was applied PRE, early POST, mid-POST, or late POST. Tolpyralate + atrazine at rates ≥30 + 1,000 g ha−1 provided equivalent control of common lambsquarters and Powell amaranth applied PRE or POST, whereas no rate applied PRE controlled common ragweed, velvetleaf, barnyardgrass, or green foxtail. Common ragweed, common lambsquarters, velvetleaf, and Powell amaranth were controlled equally regardless of POST timing. In contrast, control of barnyardgrass and green foxtail declined when herbicide application was delayed to the late-POST timing, irrespective of herbicide rate. Similarly, corn grain yield declined within each tolpyralate + atrazine rate when herbicide applications were delayed to late-POST timing. Overall, the results of this study indicate that several monocot and dicot weed species can be controlled with tolpyralate + atrazine with an early to mid-POST herbicide application timing, before weeds reach 30 cm in height, and Powell amaranth and common lambsquarters can also be controlled PRE. Additionally, this study provides further evidence highlighting the importance of effective, early-season weed control in corn.