Studies to evaluate the effect of application time of day (TOD) and protoporphyrinogen IX oxidase (PPO)-inhibiting herbicide–resistant Palmer amaranth on the efficacy of commonly used herbicides was conducted in Tennessee in 2017 and 2018. Treatments of fomesafen, lactofen, acifluorfen, paraquat, glufosinate, glufosinate plus fomesafen, paraquat plus fomesafen, and paraquat plus metribuzin were applied to PPO-resistant (PPO-R) and PPO-susceptible (PPO-S) Palmer amaranth at sunrise and midday. Control of Palmer amaranth with acifluorfen, glufosinate, and glufosinate plus fomesafen was greater with the midday application. However, control of Palmer amaranth with paraquat-based treatments was greater with the sunrise application. TOD effects on PPO-inhibiting herbicides and paraquat-based treatments were more prominent for the PPO-R Palmer amaranth biotype. The TOD effect observed when applying glufosinate in early morning hours on PPO-S Palmer amaranth can be minimized by adding fomesafen to the tank mix. However, this strategy did not provide consistent performance on PPO-R Palmer amaranth. The percentages of living Palmer amaranth plants and control were greater when paraquat plus metribuzin was applied to both biotypes. These results highlight the necessity of at least two effective herbicide sites of action for POST applications intended for controlling PPO-R Palmer amaranth. In addition, the timing of herbicide applications can affect their activity in both PPO-R and PPO-S Palmer amaranth populations.