The herbicides mesotrione and topramezone inhibit 4-hydroxyphenylpyruvate dioxygenase (HPPD) and have efficacy against smooth crabgrass. Research was conducted to determine the impacts of soil-applied nitrogen (N) fertilizer on the effectiveness of single applications of mesotrione and topramezone for postemergence smooth crabgrass control. Field experiments in 2010 and 2011 evaluated the efficacy of mesotrione (280 g a.i. ha−1) and topramezone (9 g a.i. ha−1) for control of multitiller smooth crabgrass subjected to five N fertility treatments (0, 12, 25, 37, or 49 kg N ha−1). Greenhouse experiments evaluated the response of smooth crabgrass to mesotrione (0, 70, 140, 280, 560, and 1,120 g ha−1) and topramezone (0, 4.5, 9, 18, 36, and 72 g ha−1) with 0 or 49 kg N ha−1. Further research evaluated changes in smooth crabgrass leaf tissue pigment concentrations following treatment with mesotrione (280 g ha−1) and topramezone (18 g ha−1) with 0 or 49 kg N ha−1. In field experiments, N increased smooth crabgrass control with mesotrione and topramezone for 8 wk; however, increasing N rate above 25 kg ha−1 did not improve control on any rating date. In dose-response experiments, N application reduced I50 values for mesotrione and topramezone by 67 and 53%, respectively, 21 d after treatment (DAT). Reductions in aboveground biomass with both herbicides were greater when applied following N treatment as well. In leaf-response experiments, N decreased new leaf chlorophyll and carotenoid concentrations and new leaf production after treatment with topramezone. Future research should investigate whether increased translocation of these herbicides to meristimatic regions contribute to N-enhanced efficacy.