A field experiment was conducted at the Regional Research Station, Vriddhachalam, India, during the summer of 2023, kharif 2023 and summer season of 2024 to evaluate the yield and nutrient dynamics of mechanized sesame (Sesamum indicum L.) cultivation. The experiment consisted of four crop establishment methods in the main plot: Inclined plate planter with pelletized seeds (M1), Pneumatic precision planter with pelletized seeds (M2), Pneumatic precision planter without pelletized seeds (M3) and Manual line sowing (M4) and four weed management and harvesting methods were assigned to the subplot: Quizalofop ethyl + reaper binder (S1), Quizalofop ethyl + manual harvest (S2), Hand weeding + reaper binder (S3) and Hand weeding + manual harvest (S4) in a split-plot design with three replications. Three seasonal results revealed that line sowing (M4) consistently outperformed other crop establishment techniques regarding seed and stalk yields and nutrient uptake of sesame at 30 days after sowing (DAS), 60 DAS and maturity stages. Hand weeding with either reaper binder (S3) or manual harvesting (S4) recorded the best results in sesame yield and nutrient uptake. Concerning post-harvest soil nutrient status, the crop establishment method by Pneumatic precision planter without pelletized seeds (M3) and in terms of weed management and harvesting method, Quizalofop ethyl + manual harvest (S2) recorded higher post-harvest soil available nutrient status. Hence, it is inferred that sowing sesame in lines and performing manual weeding and harvesting it either manually or using a reaper binder is the best combination that foraged the maximum nutrients and increased yields.