Two studies were conducted in 2022 and 2023 near Rocky Mount and Clayton, NC, to determine the optimal granular ammonium sulfate (AMS) rate and application timing for pyroxasulfone-coated AMS. In the rate study, AMS rates included 161, 214, 267, 321, 374, 428, and 481 kg ha−1, equivalent to 34, 45, 56, 67, 79, 90, and 101 kg N ha−1, respectively. All rates were coated with pyroxasulfone at 118 g ai ha−1 and topdressed onto 5- to 7-leaf cotton. In the timing study, pyroxasulfone (118 g ai ha−1) was coated on AMS and topdressed at 321 kg ha−1 (67 kg N ha−1) onto 5- to 7-leaf, 9- to 11-leaf, and first bloom cotton. In both studies, weed control and cotton tolerance to pyroxasulfone-coated AMS were compared to pyroxasulfone applied POST and POST-directed. The check in both studies received non-herbicide-treated AMS (321 kg ha−1). Before treatment applications, all plots (including the check) were maintained weed-free with glyphosate and glufosinate. In both studies, pyroxasulfone applied POST was most injurious (8% to 16%), while pyroxasulfone-coated AMS resulted in ≤4% injury. Additionally, no differences in cotton lint yield were observed in either study. With the exception of the lowest rate of AMS (161 kg ha−1; 79%), all AMS rates coated with pyroxasulfone controlled Palmer amaranth ≥83%, comparably to pyroxasulfone applied POST (92%) and POST-directed (89%). In the timing study, the application method did not affect Palmer amaranth control; however, applications made at the mid- and late timings outperformed early applications. These results indicate that pyroxasulfone-coated AMS can control Palmer amaranth comparably to pyroxasulfone applied POST and POST-directed, with minimal risk of cotton injury. However, the application timing could warrant additional treatment to achieve adequate late-season weed control.