A wide margin of crop safety is a desirable trait of POST herbicides, and investigation of crop tolerance is a key step in evaluation of new herbicides. Six field experiments were conducted in Ontario, Canada, from 2017 to 2018 to examine the influence of corn (Zea mays L.) hybrid (DKC42-60RIB, DKC43-47RIB, P0094AM, and P9840AM), application rate (1X and 2X), and application timing (PRE, V1, V3, and V5) on the tolerance of field corn to tolpyralate, a new 4-hydroxyphenyl pyruvate dioxygenase inhibitor, co-applied with atrazine. Two corn hybrids (DKC42-60RIB and DKC43-47RIB) exhibited slightly greater visible injury from tolpyralate + atrazine, applied POST, than P0094AM and P9840AM at 1 to 2 wk after application (WAA); hybrids responded similarly with respect to height, grain moisture, and yield. Applications of tolpyralate + atrazine at a 2X rate (80 + 2,000 g ai ha−1) induced greater injury (≤31.6%) than the field rate (40 + 1,000 g ha−1) (≤11.6%); the 2X rate applied at V1 or V3 decreased corn height and slightly increased grain moisture at harvest. On average, field rates resulted in marginally higher grain yields than 2X rates. Based on mixed-model multiple stepwise regression analysis, the air temperature at application, time of day, temperature range in the 24 h before application, and precipitation following application were useful predictor variables in estimating crop injury with tolpyralate + atrazine; however, additional environmental variables also affected crop injury. These results demonstrate the margin of corn tolerance with tolpyralate + atrazine, which provides a basis for optimization of application timing, rate, and corn hybrid selection to mitigate the risk of crop injury with this herbicide tank mixture.