Cost–benefit analysis of (iodine) biofortification at farm level is limited in the literature. This study aimed to analyze the economic feasibility of applying iodine-rich fertilizers (agronomic biofortification) to cabbage and cowpea in Northern Uganda. Data on costs and revenues were obtained from a survey of 100 farmers, and benefits that would accrue from using iodine fertilizers were elicited using consumers’ willingness to pay (WTP) for the iodine-biofortified vegetables. The cost–benefit analysis demonstrated iodine agronomic biofortification as a highly profitable effort, generating average benefit–cost ratios (BCRs) of 3.13 and 5.69 for cabbage and cowpea production, respectively, higher than the conventional production practice. However, the projective analysis showed substantive variations of economic gains from iodine biofortification among farmers, possibly due to differences in farming practices and managerial capabilities. For instance, only 74% of cabbage farmers would produce at a BCR above 1 if they were to apply iodine fertilizer. Furthermore, a sensitivity analysis to estimate the effect of subsidizing the cost of iodine fertilizer showed that a higher proportion of farmers would benefit from iodine biofortification. Therefore, as biofortification is considered a health policy intervention targeting the poor and vulnerable, farmers could be supported through fertilizer subsidies to lower the production cost of iodine-biofortified foods and to avoid passing on the price burden to vulnerable consumers.