Manganese is an important essential micronutrient, and its deficiency causes latent health issues in humans. Agronomic biofortification can promisingly improve the plant nutrient concentration without changing the genetic makeup of plants. This study was designed to assess the best method of Mn application to enhance productivity and grain Mn contents under conventional tillage (CT) and no tillage (NT) systems. Manganese was delivered through seed coating (250-mg kg−1 seed), osmopriming (0.1-M Mn solution), soil application (1 kg ha−1), and foliar application (0.25-M Mn solution). A general control with no seed Mn application was included, whereas hydropriming and water spray were used as positive control treatments for Mn seed priming and Mn foliar spray, respectively. No tillage had a higher total soil porosity (9%), soil organic carbon (16%), soil microbial biomass carbon (4%), nitrogen (2%), and soil nutrients in the CT system. Manganese nutrition through various methods significantly enhanced the yield, grain biofortification, and net benefits for CT and NT systems. Averaged across two years, the maximum improvement in grain productivity was recorded with osmopriming (28%) followed by foliar application (26%). The highest grain Mn concentration (29% over no application) was recorded with Mn foliar applications under both tillage systems. Moreover, the highest economic returns and marginal net benefits were recorded with osmopriming. To improve the wheat production, profitability, and grain Mn concentration, Mn application through priming and foliar application may be opted.