Field and greenhouse experiments were conducted in Nebraska to (1) confirm the 4-hydroxyphenylpyruvate dioxygenase (HPPD)-inhibiting resistant-waterhemp biotype (HPPD-RW) by quantifying the resistance levels in dose-response studies, and (2) to evaluate efficacy of PRE-only, POST-only, and PRE followed by POST herbicide programs for control of HPPD-RW in corn. Greenhouse dose-response studies confirmed that the suspected waterhemp biotype in Nebraska has evolved resistance to HPPD-inhibiting herbicides with a 2- to 18-fold resistance depending upon the type of HPPD-inhibiting herbicide being sprayed. Under field conditions, at 56 d after treatment, ≥90% control of the HPPD-RW was achieved with PRE-applied mesotrione/atrazine/S-metolachlor+acetochlor, pyroxasulfone (180 and 270 g ai ha−1), pyroxasulfone/fluthiacet-methyl/atrazine, and pyroxasulfone+saflufenacil+atrazine. Among POST-only herbicide programs, glyphosate, a premix of mesotrione/atrazine tank-mixed with diflufenzopyr/dicamba, or metribuzin, or glufosinate provided ≥92% HPPD-RW control. Herbicide combinations of different effective sites of action in mixtures provided ≥86% HPPD-RW control in PRE followed by POST herbicide programs. It is concluded that the suspected waterhemp biotype is resistant to HPPD-inhibiting herbicides and alternative herbicide programs are available for effective control in corn. The occurrence of HPPD-RW in Nebraska is significant because it limits the effectiveness of HPPD-inhibiting herbicides.