Integrated input for crop productivity can increase food security among smallholder farming systems. The study evaluated agronomic and economic response of four input bundle treatments on five soybean [Glycine max (L.) Merr.] cultivars conducted under rain-fed conditions over a 4-yr period in Ghana. Experiments were a randomized complete block in factorial arrangement with four replications. Input bundles were NoduMax inoculant (I), phosphorus application (P), inoculated seed followed by phosphorus application (I+P), and certified seed as control treatment. Cultivars were Afayak, Jenguma, Quarshie, Songda, and Suong-Pungun. Soils were moderately acidic (5.7 pH) with macroand micronutrient deficiencies. Grain yield, mean gross margin (MGM), and benefit-cost ratio (BCR) for input bundles were in descending order I+P bundle > P bundle > I bundle > control. Yield was greater in I+P bundle over I bundle, P bundle, and control by 27, 16, and 65%, respectively. Grain yield, MGM, and BCR in descending cultivar order were Afayak > Jenguma > Suong-Pungun > Quarshie > Songda. Grain yield was greater in Afayak over Jenguma, Suong-Pungun, Quarshie, and Songda by 3, 11, 13, and 21%, respectively. Cultivar yield differences may be genetically driven. This study suggests smallholders can benefit from increased returns from inoculation + phosphorus synergy. The results indicate that low soybean yields in smallholder farms are not the result of high input cost or low prices but rather are due to the inability of farmers to shift from low input productivity to innovative production technologies. Integrating soybean as a commercial crop within staple crops of smallholder farmers can provide additional income and nutrition for households. Abbreviations: BCR, benefit-cost ratio; MGM, mean gross margin. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.