Twenty-seven field experiments were conducted from 2015-2018 at nine locations to evaluate tolpyralate, a new pyrazolone 4-hydroxyphenyl-pyruvate dioxygenase inhibitor, for weed management in corn. The biologically-effective dose of tolpyralate and tolpyralate + atrazine was established in eight common annual weed species, and separately in multiple herbicide-resistant (MR) Canada fleabane and waterhemp biotypes. Co-application of tolpyralate with atrazine improved weed control; tolpyralate + atrazine at label rates provided similar or improved control of eight common weed species, MR Canada fleabane and MR waterhemp compared to industry standards. Four weed species were controlled equally regardless of POST application timing and two species were controlled with tolpyralate + atrazine applied pre-emergence; annual grass control declined with delayed applications. Corn was at greatest risk of injury with tolpyralate + atrazine applied at V1 or V3, and at 2X rates. Injury was influenced by environmental variables, but did not translate to grain yield loss.