Weeds impose significant challenges in maize production, leading to decreased grain yield and profit. The crop-weed competition for plant's required resources like light, water and nutrients, ultimately hinders maize growth and yield. To address this concern, field experiments were conducted for two years (Kharif 2021 and 2022) at the Experimental Farm, Annamalai University, Annamalai Nagar, India and compared the effects of hand weeding with those of sequential and sole application of Pre-Emergence (PE) and Post-Emergence (PoE) herbicides in maize. The experiment was designed under a randomized complete block design with three replications and nine treatments. The treatments consisted of unweeded control (T1), hand weeding twice at 15 and 30 Days After Sowing (DAS) (T2), PE application of atrazine at 1 kg a.i ha-1 on 3 DAS (T3), PoE application of topramezone at 25.2 g a.i ha-1 on 18 DAS (T4), PoE application of tembotrione at 120 g a.i ha-1 on 18 DAS (T5), PoE application of halosulfuron methyl at 67.5 g a.i ha-1 on 18 DAS (T6), PE application of atrazine at 1 kg a.i ha-1 on 3 DAS + PoE application of topramezone at 25.2 g a.i ha-1 on 18 DAS (T7), PE application of atrazine at 1 kg a.i ha-1 on 3 DAS + PoE application of tembotrione at 120 g a.i ha-1 on 18 DAS (T8) and PE application of atrazine at 1 kg a.i ha-1 on 3 DAS + PoE application of halosulfuron methyl at 67.5 g a.i ha-1 on 18 DAS (T9). The results indicated that hand weeding twice at 15 and 25 DAS recorded significantly superior weed control efficiency (89.82 and 83.31 %), weed control index (90.11 and 87.87 %), maize growth attributes and grain yield (6732 and 6831 kg ha-1) and stover yield (10920 and 11071 kg ha-1) during the years 2021 and 2022 respectively. However, it was on par with PE application of atrazine at 1 kg a.i ha-1 on 3 DAS + PoE application of topramezone at 25.2 g a.i ha-1/tembotrione at 120 g a.i ha-1on 18 DAS. This suppressed the weeds nutrient uptake and enhanced nutrient uptake by maize. Thus, lower post-harvest actual balance and net gain of soil available nutrients were noticed with these treatments. Concerning economics, PE application of atrazine at 1 kg a.i ha-1 on 3 DAS + PoE application of topramezone at 25.2 g a.i ha-1 on 18 DAS may offer a more effective way to increase profitability in maize cultivation.