A field experiment was conducted during the Kharif seasons of 2021 and 2022 to evaluate the optimal chemical weed management strategies for maize cultivation. The experiment employed a randomized block design with 14 distinct treatments, each replicated three times, involving pre-emergence (PRE) and post-emergence (PoE) applications of herbicides, including pendimethalin, atrazine, tembotrione, topramezone, halosulfuron, mesotrons, and 2,4-D, either alone or in combination. The results indicated that hand weeding twice (20 and 40 DAS) resulted in the lowest total weed density at 30 DAS (84.70% and 82.75%, respectively) and dry matter at 30 DAS (96.79% and 95.89%, respectively) during Kharif 2021 and 2022, followed by tembotrione post-emergence and hand weeding at 20 DAS. Grain yield was significantly higher (54.6 and 55.1 q/ha, respectively) with weed-free treatment than all other treatments; however, it was statistically at par with treatments T12, T11, T8, T7, T6, T5, and T4 during Kharif 2021 and 2022, followed by atrazine 1.5 kg/ha as PE fb tembotrione 120 g/ha at 20 DAS (52.9 and 53.9 q/ha, respectively). The random forest model (RFM) exhibited exceptional predictive accuracy for yield, with an R² value exceeding 0.85, identifying the test weight and grain per cob as the most significant predictors. The study concluded that specific herbicide combinations can effectively manage weed populations while enhancing maize productivity, but integrating cultural practices with herbicide use could provide a more balanced and sustainable approach to weed management.