To achieve the nutritional target of human food, boron (B) has been described as an essential mineral in determining seed and theoretical oil yield of Sesamum indicum L. The research to increase its cultivation is garnering attention due to its high oil content, quality and its utilization for various purposes, which include human nutrition as well as its use in the food industry. For this, a two-year field experiment was performed at PAU, Punjab, India to determine the effect of different concentrations of foliar-applied B (20, 30 and 40 mg L−1) and different growth stages of crop, i.e., we measured the effects on agroeconomic indicators and certain quality parameters of sesame using different concentrations of B applied at the flowering and capsule formation stages as compared to using water spray and untreated plants. Water spray did not significantly affect the studied parameters. However, B application significantly increased the yield, uptake, antioxidant activity (AOA) and theoretical oil content (TOC) compared to those of untreated plants. The maximum increase in seed yield (26.75%), B seed and stover uptake (64.08% and 69.25%, respectively) as well as highest AOA (69.41%) and benefit to cost ratio (B:C ratio 2.63) was recorded when B was applied at 30 mg L−1 at the flowering and capsule formation stages. However, the maximum sesame yield and B uptake were recorded when B was applied at a rate of 30 mg L−1. A significant increase in TOC was also recorded with a B application rate of 30 mg L−1. For efficiency indices, the higher values of boron agronomic efficiency (BAE) and boron crop recovery efficiency (BCRE) were recorded when B was applied at 20 mg L−1 (5.25 and 30.56, respectively) and 30 mg L−1 (4.96 and 26.11, respectively) at the flowering and capsule formation stages. In conclusion, application of B @ 30 mg L−1 at the flowering and capsule formation stages seemed a viable technique to enhance yield, B uptake and economic returns of sesame.