Manganese (Mn) is one important microelement for plants and the human beings. This study was conducted to evaluate the potential of Mn nutrition in improving the productivity and grain biofortification of wheat. For optimization of Mn seed treatments, seeds were primed with 0.1 and 0.01 M Mn solution, or were coated with 250 and 500 mg Mn kg−1 seed. The optimized treatments were used in the second experiment replicated over time and space. In the first experiment conducted at Faisalabad during 2012–2013, maximum grain yield was recorded with Mn seed priming (0.1 M Mn solution), while maximum grain Mn concentration was recorded with foliar application of 0.75 M Mn solution and seed coating with 250 mg Mn kg−1 seed. In the second experiment, conducted at Faisalabad and Sheikhupura during 2013–2014, and at Faisalabad during 2014–2015, maximum grain yield and grain Mn concentration were recorded from seed priming with 0.1 M Mn solution. Regardless of method, Mn application improved the productivity and grain biofortification of wheat. Overall order of improvement in grain yield was seed priming (3.87 Mg ha−1) > foliar application (3.74 Mg ha−1) > seed coating (3.57 Mg ha−1). Regarding grain Mn concentration, the best treatment was seed priming (41.40 µg g−1) followed by seed coating (39.87 µg g−1) and foliar application (36.94 µg g−1). Maximum net returns and benefit-cost ratio were obtained with Mn seed priming, while maximum marginal rate of return was obtained with Mn seed coating. In conclusion, Mn application through seed treatments was cost effective for improving the productivity and grain biofortification of bread wheat in alkaline calcareous soil.